Social Influences on Neurobiology and Behavior: Epigenetic Effects During Development

PubMed Central

Curley, JP; Jensen, CL; Mashoodh, R; Champagne, FA

2010-01-01

The quality of the social environment can have profound influences on the development and activity of neural systems with implications for numerous behavioral and physiological responses, including the expression of emotionality. Though social experiences occurring early in development may be particularly influential on the developing brain, there is continued plasticity within these neural circuits amongst juveniles and into early adulthood. In this review, we explore the evidence derived from studies in rodents which illustrates the social modulation during development of neural systems, with a particular emphasis on those systems in which a long-term effect is observed. One possible explanation for the persistence of dynamic changes in these systems in response to the environment is the involvement of epigenetic mechanisms, and here we discuss recent studies which support the role of these mechanisms in mediating the link between social experiences, gene expression, neurobiological changes, and behavioral variation. This literature raises critical questions about the interaction between neural systems, the concordance between neural and behavioral changes, sexual dimorphism in effects, the importance of considering individual differences in response to the social environment, and the potential of an epigenetic perspective in advancing our understanding of the pathways leading to variations in mental health. PMID:20650569

Characterization of Early Cortical Neural Network Development in Multiwell Microelectrode Array Plates

EPA Science Inventory

We examined the development of neural network activity using microelectrode array (MEA) recordings made in multi-well MEA plates (mwMEAs) over the first 12 days in vitro (DIV). In primary cortical cultures made from postnatal rats, action potential spiking activity was essentiall...

PSD-95 is post-transcriptionally repressed during early neural development by PTBP1 and PTBP2.

PubMed

Zheng, Sika; Gray, Erin E; Chawla, Geetanjali; Porse, Bo Torben; O'Dell, Thomas J; Black, Douglas L

2012-01-15

Postsynaptic density protein 95 (PSD-95) is essential for synaptic maturation and plasticity. Although its synaptic regulation has been widely studied, the control of PSD-95 cellular expression is not understood. We found that Psd-95 was controlled post-transcriptionally during neural development. Psd-95 was transcribed early in mouse embryonic brain, but most of its product transcripts were degraded. The polypyrimidine tract binding proteins PTBP1 and PTBP2 repressed Psd-95 (also known as Dlg4) exon 18 splicing, leading to premature translation termination and nonsense-mediated mRNA decay. The loss of first PTBP1 and then of PTBP2 during embryonic development allowed splicing of exon 18 and expression of PSD-95 late in neuronal maturation. Re-expression of PTBP1 or PTBP2 in differentiated neurons inhibited PSD-95 expression and impaired the development of glutamatergic synapses. Thus, expression of PSD-95 during early neural development is controlled at the RNA level by two PTB proteins whose sequential downregulation is necessary for synapse maturation.

21 CFR 101.79 - Health claims: Folate and neural tube defects.

Code of Federal Regulations, 2013 CFR

2013-04-01

... result in infant mortality or serious disability. The birth defects anencephaly and spina bifida are the... development. Because the neural tube forms and closes during early pregnancy, the defect may occur before a... pregnancy had a reduced risk of having a child with a neural tube defect. (Products containing this level of...

21 CFR 101.79 - Health claims: Folate and neural tube defects.

Code of Federal Regulations, 2014 CFR

2014-04-01

... result in infant mortality or serious disability. The birth defects anencephaly and spina bifida are the... development. Because the neural tube forms and closes during early pregnancy, the defect may occur before a... pregnancy had a reduced risk of having a child with a neural tube defect. (Products containing this level of...

21 CFR 101.79 - Health claims: Folate and neural tube defects.

Code of Federal Regulations, 2012 CFR

2012-04-01

... result in infant mortality or serious disability. The birth defects anencephaly and spina bifida are the... development. Because the neural tube forms and closes during early pregnancy, the defect may occur before a... pregnancy had a reduced risk of having a child with a neural tube defect. (Products containing this level of...

Application of neural networks to software quality modeling of a very large telecommunications system.

PubMed

Khoshgoftaar, T M; Allen, E B; Hudepohl, J P; Aud, S J

1997-01-01

Society relies on telecommunications to such an extent that telecommunications software must have high reliability. Enhanced measurement for early risk assessment of latent defects (EMERALD) is a joint project of Nortel and Bell Canada for improving the reliability of telecommunications software products. This paper reports a case study of neural-network modeling techniques developed for the EMERALD system. The resulting neural network is currently in the prototype testing phase at Nortel. Neural-network models can be used to identify fault-prone modules for extra attention early in development, and thus reduce the risk of operational problems with those modules. We modeled a subset of modules representing over seven million lines of code from a very large telecommunications software system. The set consisted of those modules reused with changes from the previous release. The dependent variable was membership in the class of fault-prone modules. The independent variables were principal components of nine measures of software design attributes. We compared the neural-network model with a nonparametric discriminant model and found the neural-network model had better predictive accuracy.

Environmental estrogens alter early development in Xenopus laevis.

PubMed

Bevan, Cassandra L; Porter, Donna M; Prasad, Anita; Howard, Marthe J; Henderson, Leslie P

2003-04-01

A growing number of environmental toxicants found in pesticides, herbicides, and industrial solvents are believed to have deleterious effects on development by disrupting hormone-sensitive processes. We exposed Xenopus laevis embryos at early gastrula to the commonly encountered environmental estrogens nonylphenol, octylphenol, and methoxychlor, the antiandrogen, p,p-DDE, or the synthetic androgen, 17 alpha-methyltestosterone at concentrations ranging from 10 nM to 10 microM and examined them at tailbud stages (approximately 48 hr of treatment). Exposure to the three environmental estrogens, as well as to the natural estrogen 17 beta-estradiol, increased mortality, induced morphologic deformations, increased apoptosis, and altered the deposition and differentiation of neural crest-derived melanocytes in tailbud stage embryos. Although neural crest-derived melanocytes were markedly altered in embryos treated with estrogenic toxicants, expression of the early neural crest maker Xslug, a factor that regulates both the induction and subsequent migration of neural crest cells, was not affected, suggesting that the disruption induced by these compounds with respect to melanocyte development may occur at later stages of their differentiation. Co-incubation of embryos with the pure antiestrogen ICI 182,780 blocked the ability of nonylphenol to induce abnormalities in body shape and in melanocyte differentiation but did not block the effects of methoxychlor. Our data indicate not only that acute exposure to these environmental estrogens induces deleterious effects on early vertebrate development but also that different environmental estrogens may alter the fate of a specific cell type via different mechanisms. Finally, our data suggest that the differentiation of neural crest-derived melanocytes may be particularly sensitive to the disruptive actions of these ubiquitous chemical contaminants.

[Early warning on measles through the neural networks].

PubMed

Yu, Bin; Ding, Chun; Wei, Shan-bo; Chen, Bang-hua; Liu, Pu-lin; Luo, Tong-yong; Wang, Jia-gang; Pan, Zhi-wei; Lu, Jun-an

2011-01-01

To discuss the effects on early warning of measles, using the neural networks. Based on the available data through monthly and weekly reports on measles from January 1986 to August 2006 in Wuhan city. The modal was developed using the neural networks to predict and analyze the prevalence and incidence of measles. When the dynamic time series modal was established with back propagation (BP) networks consisting of two layers, if p was assigned as 9, the convergence speed was acceptable and the correlation coefficient was equal to 0.85. It was more acceptable for monthly forecasting the specific value, but better for weekly forecasting the classification under probabilistic neural networks (PNN). When data was big enough to serve the purpose, it seemed more feasible for early warning using the two-layer BP networks. However, when data was not enough, then PNN could be used for the purpose of prediction. This method seemed feasible to be used in the system for early warning.

Bi-Parental Care Contributes to Sexually Dimorphic Neural Cell Genesis in the Adult Mammalian Brain

PubMed Central

Mak, Gloria K.; Antle, Michael C.; Dyck, Richard H.; Weiss, Samuel

2013-01-01

Early life events can modulate brain development to produce persistent physiological and behavioural phenotypes that are transmissible across generations. However, whether neural precursor cells are altered by early life events, to produce persistent and transmissible behavioural changes, is unknown. Here, we show that bi-parental care, in early life, increases neural cell genesis in the adult rodent brain in a sexually dimorphic manner. Bi-parentally raised male mice display enhanced adult dentate gyrus neurogenesis, which improves hippocampal neurogenesis-dependent learning and memory. Female mice display enhanced adult white matter oligodendrocyte production, which increases proficiency in bilateral motor coordination and preference for social investigation. Surprisingly, single parent-raised male and female offspring, whose fathers and mothers received bi-parental care, respectively, display a similar enhancement in adult neural cell genesis and phenotypic behaviour. Therefore, neural plasticity and behavioural effects due to bi-parental care persist throughout life and are transmitted to the next generation. PMID:23650527

Mammalian Target of Rapamycin: Its Role in Early Neural Development and in Adult and Aged Brain Function

PubMed Central

Garza-Lombó, Carla; Gonsebatt, María E.

2016-01-01

The kinase mammalian target of rapamycin (mTOR) integrates signals triggered by energy, stress, oxygen levels, and growth factors. It regulates ribosome biogenesis, mRNA translation, nutrient metabolism, and autophagy. mTOR participates in various functions of the brain, such as synaptic plasticity, adult neurogenesis, memory, and learning. mTOR is present during early neural development and participates in axon and dendrite development, neuron differentiation, and gliogenesis, among other processes. Furthermore, mTOR has been shown to modulate lifespan in multiple organisms. This protein is an important energy sensor that is present throughout our lifetime its role must be precisely described in order to develop therapeutic strategies and prevent diseases of the central nervous system. The aim of this review is to present our current understanding of the functions of mTOR in neural development, the adult brain and aging. PMID:27378854

Neural crest cells: from developmental biology to clinical interventions.

PubMed

Noisa, Parinya; Raivio, Taneli

2014-09-01

Neural crest cells are multipotent cells, which are specified in embryonic ectoderm in the border of neural plate and epiderm during early development by interconnection of extrinsic stimuli and intrinsic factors. Neural crest cells are capable of differentiating into various somatic cell types, including melanocytes, craniofacial cartilage and bone, smooth muscle, and peripheral nervous cells, which supports their promise for cell therapy. In this work, we provide a comprehensive review of wide aspects of neural crest cells from their developmental biology to applicability in medical research. We provide a simplified model of neural crest cell development and highlight the key external stimuli and intrinsic regulators that determine the neural crest cell fate. Defects of neural crest cell development leading to several human disorders are also mentioned, with the emphasis of using human induced pluripotent stem cells to model neurocristopathic syndromes. © 2014 Wiley Periodicals, Inc.

The Relationship between Early Neural Responses to Emotional Faces at Age 3 and Later Autism and Anxiety Symptoms in Adolescents with Autism

ERIC Educational Resources Information Center

Neuhaus, Emily; Jones, Emily J. H.; Barnes, Karen; Sterling, Lindsey; Estes, Annette; Munson, Jeff; Dawson, Geraldine; Webb, Sara J.

2016-01-01

Both autism spectrum (ASD) and anxiety disorders are associated with atypical neural and attentional responses to emotional faces, differing in affective face processing from typically developing peers. Within a longitudinal study of children with ASD (23 male, 3 female), we hypothesized that early ERPs to emotional faces would predict concurrent…

Antagonism between the transcription factors NANOG and OTX2 specifies rostral or caudal cell fate during neural patterning transition.

PubMed

Su, Zhenghui; Zhang, Yanqi; Liao, Baojian; Zhong, Xiaofen; Chen, Xin; Wang, Haitao; Guo, Yiping; Shan, Yongli; Wang, Lihui; Pan, Guangjin

2018-03-23

During neurogenesis, neural patterning is a critical step during which neural progenitor cells differentiate into neurons with distinct functions. However, the molecular determinants that regulate neural patterning remain poorly understood. Here we optimized the "dual SMAD inhibition" method to specifically promote differentiation of human pluripotent stem cells (hPSCs) into forebrain and hindbrain neural progenitor cells along the rostral-caudal axis. We report that neural patterning determination occurs at the very early stage in this differentiation. Undifferentiated hPSCs expressed basal levels of the transcription factor orthodenticle homeobox 2 (OTX2) that dominantly drove hPSCs into the "default" rostral fate at the beginning of differentiation. Inhibition of glycogen synthase kinase 3β (GSK3β) through CHIR99021 application sustained transient expression of the transcription factor NANOG at early differentiation stages through Wnt signaling. Wnt signaling and NANOG antagonized OTX2 and, in the later stages of differentiation, switched the default rostral cell fate to the caudal one. Our findings have uncovered a mutual antagonism between NANOG and OTX2 underlying cell fate decisions during neural patterning, critical for the regulation of early neural development in humans. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Neural mirroring and social interaction: Motor system involvement during action observation relates to early peer cooperation.

PubMed

Endedijk, H M; Meyer, M; Bekkering, H; Cillessen, A H N; Hunnius, S

2017-04-01

Whether we hand over objects to someone, play a team sport, or make music together, social interaction often involves interpersonal action coordination, both during instances of cooperation and entrainment. Neural mirroring is thought to play a crucial role in processing other's actions and is therefore considered important for social interaction. Still, to date, it is unknown whether interindividual differences in neural mirroring play a role in interpersonal coordination during different instances of social interaction. A relation between neural mirroring and interpersonal coordination has particularly relevant implications for early childhood, since successful early interaction with peers is predictive of a more favorable social development. We examined the relation between neural mirroring and children's interpersonal coordination during peer interaction using EEG and longitudinal behavioral data. Results showed that 4-year-old children with higher levels of motor system involvement during action observation (as indicated by lower beta-power) were more successful in early peer cooperation. This is the first evidence for a relation between motor system involvement during action observation and interpersonal coordination during other instances of social interaction. The findings suggest that interindividual differences in neural mirroring are related to interpersonal coordination and thus successful social interaction. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Development of a neural network for early detection of renal osteodystrophy

NASA Astrophysics Data System (ADS)

Cheng, Shirley N.; Chan, Heang-Ping; Adler, Ronald; Niklason, Loren T.; Chang, Chair-Li

1991-07-01

Bone erosion presenting as subperiosteal resorption on the phalanges of the hand is an early manifestation of hyperparathyroidism associated with chronic renal failure. At present, the diagnosis is made by trained radiologists through visual inspection of hand radiographs. In this study, a neural network is being developed to assess the feasibility of computer-aided detection of these changes. A two-pass approach is adopted. The digitized image is first compressed by a Laplacian pyramid compact code. The first neural network locates the region of interest using vertical projections along the phalanges and then the horizontal projections across the phalanges. A second neural network is used to classify texture variations of trabecular patterns in the region using a concurrence matrix as the input to a two-dimensional sensor layer to detect the degree of associated osteopenia. Preliminary results demonstrate the feasibility of this approach.

Blastomere biopsy influences epigenetic reprogramming during early embryo development, which impacts neural development and function in resulting mice.

PubMed

Wu, Yibo; Lv, Zhuo; Yang, Yang; Dong, Guoying; Yu, Yang; Cui, Yiqiang; Tong, Man; Wang, Liu; Zhou, Zuomin; Zhu, Hui; Zhou, Qi; Sha, Jiahao

2014-05-01

Blastomere biopsy is used in preimplantation genetic diagnosis; however, the long-term implications on the offspring are poorly characterized. We previously reported a high risk of memory defects in adult biopsied mice. Here, we assessed nervous function of aged biopsied mice and further investigated the mechanism of neural impairment after biopsy. We found that aged biopsied mice had poorer spatial learning ability, increased neuron degeneration, and altered expression of proteins involved in neural degeneration or dysfunction in the brain compared to aged control mice. Furthermore, the MeDIP assay indicated a genome-wide low methylation in the brains of adult biopsied mice when compared to the controls, and most of the genes containing differentially methylated loci in promoter regions were associated with neural disorders. When we further compared the genomic DNA methylation profiles of 7.5-days postconception (dpc) embryos between the biopsy and control group, we found the whole genome low methylation in the biopsied group, suggesting that blastomere biopsy was an obstacle to de novo methylation during early embryo development. Further analysis on mRNA profiles of 4.5-dpc embryos indicated that reduced expression of de novo methylation genes in biopsied embryos may impact de novo methylation. In conclusion, we demonstrate an abnormal neural development and function in mice generated after blastomere biopsy. The impaired epigenetic reprogramming during early embryo development may be the latent mechanism contributing to the impairment of the nervous system in the biopsied mice, which results in a hypomethylation status in their brains.

Auditory Processing in Noise: A Preschool Biomarker for Literacy.

PubMed

White-Schwoch, Travis; Woodruff Carr, Kali; Thompson, Elaine C; Anderson, Samira; Nicol, Trent; Bradlow, Ann R; Zecker, Steven G; Kraus, Nina

2015-07-01

Learning to read is a fundamental developmental milestone, and achieving reading competency has lifelong consequences. Although literacy development proceeds smoothly for many children, a subset struggle with this learning process, creating a need to identify reliable biomarkers of a child's future literacy that could facilitate early diagnosis and access to crucial early interventions. Neural markers of reading skills have been identified in school-aged children and adults; many pertain to the precision of information processing in noise, but it is unknown whether these markers are present in pre-reading children. Here, in a series of experiments in 112 children (ages 3-14 y), we show brain-behavior relationships between the integrity of the neural coding of speech in noise and phonology. We harness these findings into a predictive model of preliteracy, revealing that a 30-min neurophysiological assessment predicts performance on multiple pre-reading tests and, one year later, predicts preschoolers' performance across multiple domains of emergent literacy. This same neural coding model predicts literacy and diagnosis of a learning disability in school-aged children. These findings offer new insight into the biological constraints on preliteracy during early childhood, suggesting that neural processing of consonants in noise is fundamental for language and reading development. Pragmatically, these findings open doors to early identification of children at risk for language learning problems; this early identification may in turn facilitate access to early interventions that could prevent a life spent struggling to read.

Infancy and Early Childhood: Opportunities and Risks for Pennsylvania and Its Children. A Special Report.

ERIC Educational Resources Information Center

Pennsylvania Partnerships for Children, Harrisburg.

This Kids Count special report examines brain development during infancy and early childhood in order to provide a basis for an informed discussion about the need for preventive programs to foster healthy child development. The report summarizes information on early brain development and how experience shapes neural connections. It focuses on the…

Zebrafish msxB, msxC and msxE function together to refine the neural-nonneural border and regulate cranial placodes and neural crest development.

PubMed

Phillips, Bryan T; Kwon, Hye-Joo; Melton, Colt; Houghtaling, Paul; Fritz, Andreas; Riley, Bruce B

2006-06-15

The zebrafish muscle segment homeobox genes msxB, msxC and msxE are expressed in partially overlapping domains in the neural crest and preplacodal ectoderm. We examined the roles of these msx genes in early development. Disrupting individual msx genes causes modest variable defects, whereas disrupting all three produces a reproducible severe phenotype, suggesting functional redundancy. Neural crest differentiation is blocked at an early stage. Preplacodal development begins normally, but placodes arising from the msx expression domain later show elevated apoptosis and are reduced in size. Cell proliferation is normal in these tissues. Unexpectedly, Msx-deficient embryos become ventralized by late gastrulation whereas misexpression of msxB dorsalizes the embryo. These effects appear to involve Distal-less (Dlx) protein activity, as loss of dlx3b and dlx4b suppresses ventralization in Msx-depleted embryos. At the same time, Msx-depletion restores normal preplacodal gene expression to dlx3b-dlx4b mutants. These data suggest that mutual antagonism between Msx and Dlx proteins achieves a balance of function required for normal preplacodal differentiation and placement of the neural-nonneural border.

Disrupted neural synchronization in toddlers with autism

PubMed Central

Dinstein, Ilan; Pierce, Karen; Eyler, Lisa; Solso, Stephanie; Malach, Rafael; Behrmann, Marlene; Courchesne, Eric

2011-01-01

Summary Autism is often described as a disorder of neural synchronization. However, it is unknown how early in development synchronization abnormalities emerge and whether they are related to the development of early autistic behavioral symptoms. Here, we show that disrupted synchronization is evident in the spontaneous cortical activity of naturally sleeping toddlers with autism, but not in toddlers with language delay or typical development. Toddlers with autism exhibited significantly weaker inter-hemispheric synchronization (i.e. weak “functional connectivity” across the two hemispheres) in putative language areas. The strength of synchronization was positively correlated with verbal ability, negatively correlated with autism severity, and enabled identification of the majority of autistic toddlers (72%) with high accuracy (84%). Disrupted cortical synchronization, therefore, appears to be a notable characteristic of autism neurophysiology that is evident at very early stages of autism development. PMID:21689606

Feed Your Head: Neurodevelopmental Control of Feeding and Metabolism

PubMed Central

Lee, Daniel A.; Blackshaw, Seth

2014-01-01

During critical periods of development early in life, excessive or scarce nutritional environments can disrupt the development of central feeding and metabolic neural circuitry, leading to obesity and metabolic disorders in adulthood. A better understanding of the genetic networks that control the development of feeding and metabolic neural circuits, along with knowledge of how and where dietary signals disrupt this process, can serve as the basis for future therapies aimed at reversing the public health crisis that is now building as a result of the global obesity epidemic. This review of animal and human studies highlights recent insights into the molecular mechanisms that regulate the development of central feeding circuitries, the mechanisms by which gestational and early postnatal nutritional status affects this process, and approaches aimed at counteracting the deleterious effects of early over- and underfeeding. PMID:24274739

The effect of flurbiprofen on the development of anencephaly in early stage chicken embryos.

PubMed

Özeren, Ersin; Er, Uygur; Güvenç, Yahya; Demirci, Adnan; Arıkök, Ata Türker; Şenveli, Engin; Ergün, Rüçhan Behzat

2015-04-01

The study investigated the effect of flurbiprofen on the development of anencephaly in early stage chicken embryos. We looked at four groups with a total of 36 embryos. There was a control group, a normal saline group, a normal-dose group and a high-dose group with ten, ten, eight and eight eggs with embryo respectively. Two embryos in the control group, studied with light microscopy at 48 h, were consistent with 28-29 hours' incubation in the Hamburger-Hamilton System. They had open neural tubes. The other embryos in this group were considered normal. One embryo in the normal saline group was on the occlusion stage at 48 h. One embryo showed an open neural tube. They were compatible with 28-29 hours' incubation in the Hamburger-Hamilton system. The remaining eight embryos showed normal development. In the normal dose group, one embryo showed underdevelopment of the embryonic disc and the embryo was dead. In four embryos, the neural tubes were open. One cranial malformation was found that was complicated with anencephaly in one embryo. In two embryos the neural tubes were closed, as they showed normal development, and they reached their expected stages according to the Hamburger-Hamilton classification. There was no malformation or growth retardation. Four experimental embryos were anencephalic in the high dose group, and three embryos had open neural tubes. One embryo exhibited both anencephaly and a neural tube closure defect. None of the embryos in this group showed normal development. Even the usual therapeutic doses of flurbiprofen increased the risk of neural tube defect. Flurbiprofen was found to significantly increase the risk of anencephaly. The provision of improved technical materials and studies with larger sample sizes will reveal the stage of morphological disruption during the development of embryos.

Anomalous Development of Brain Structure and Function in Spina Bifida Myelomeningocele

ERIC Educational Resources Information Center

Juranek, Jenifer; Salman, Michael S.

2010-01-01

Spina bifida myelomeningocele (SBM) is a specific type of neural tube defect whereby the open neural tube at the level of the spinal cord alters brain development during early stages of gestation. Some structural anomalies are virtually unique to individuals with SBM, including a complex pattern of cerebellar dysplasia known as the Chiari II…

Imidacloprid Exposure Suppresses Neural Crest Cells Generation during Early Chick Embryo Development.

PubMed

Wang, Chao-Jie; Wang, Guang; Wang, Xiao-Yu; Liu, Meng; Chuai, Manli; Lee, Kenneth Ka Ho; He, Xiao-Song; Lu, Da-Xiang; Yang, Xuesong

2016-06-15

Imidacloprid is a neonicotinoid pesticide that is widely used in the control pests found on crops and fleas on pets. However, it is still unclear whether imidacloprid exposure could affect early embryo development-despite some studies having been conducted on the gametes. In this study, we demonstrated that imidacloprid exposure could lead to abnormal craniofacial osteogenesis in the developing chick embryo. Cranial neural crest cells (NCCs) are the progenitor cells of the chick cranial skull. We found that the imidacloprid exposure retards the development of gastrulating chick embryos. HNK-1, PAX7, and Ap-2α immunohistological stainings indicated that cranial NCCs generation was inhibited after imidacloprid exposure. Double immunofluorescent staining (Ap-2α and PHIS3 or PAX7 and c-Caspase3) revealed that imidacloprid exposure inhibited both NCC proliferation and apoptosis. In addition, it inhibited NCCs production by repressing Msx1 and BMP4 expression in the developing neural tube and by altering expression of EMT-related adhesion molecules (Cad6B, E-Cadherin, and N-cadherin) in the developing neural crests. We also determined that imidacloprid exposure suppressed cranial NCCs migration and their ability to differentiate. In sum, we have provided experimental evidence that imidacloprid exposure during embryogenesis disrupts NCCs development, which in turn causes defective cranial bone development.

A developmental perspective on the neural bases of human empathy.

PubMed

Tousignant, Béatrice; Eugène, Fanny; Jackson, Philip L

2017-08-01

While empathy has been widely studied in philosophical and psychological literatures, recent advances in social neuroscience have shed light on the neural correlates of this complex interpersonal phenomenon. In this review, we provide an overview of brain imaging studies that have investigated the neural substrates of human empathy. Based on existing models of the functional architecture of empathy, we review evidence of the neural underpinnings of each main component, as well as their development from infancy. Although early precursors of affective sharing and self-other distinction appear to be present from birth, recent findings also suggest that even higher-order components of empathy such as perspective-taking and emotion regulation demonstrate signs of development during infancy. This merging of developmental and social neuroscience literature thus supports the view that ontogenic development of empathy is rooted in early infancy, well before the emergence of verbal abilities. With age, the refinement of top-down mechanisms may foster more appropriate empathic responses, thus promoting greater altruistic motivation and prosocial behaviors. Copyright © 2016 Elsevier Inc. All rights reserved.

Regional differences in the expression of laminin isoforms during mouse neural tube development

PubMed Central

Copp, Andrew J.; Carvalho, Rita; Wallace, Adam; Sorokin, Lydia; Sasaki, Takako; Greene, Nicholas D.E.; Ybot-Gonzalez, Patricia

2013-01-01

Many significant human birth defects originate around the time of neural tube closure or early during post-closure nervous system development. For example, failure of the neural tube to close generates anencephaly and spina bifida, faulty cell cycle progression is implicated in primary microcephaly, while defective migration of neuroblasts can lead to neuronal migration disorders such as lissencephaly. At the stage of neural tube closure, basement membranes are becoming organised around the neuroepithelium, and beneath the adjacent non-neural surface ectoderm. While there is circumstantial evidence to implicate basement membrane dynamics in neural tube and surface ectodermal development, we have an incomplete understanding of the molecular composition of basement membranes at this stage. In the present study, we examined the developing basement membranes of the mouse embryo at mid-gestation (embryonic day 9.5), with particular reference to laminin composition. We performed in situ hybridization to detect the mRNAs of all eleven individual laminin chains, and immunohistochemistry to identify which laminin chains are present in the basement membranes. From this information, we inferred the likely laminin variants and their tissues of origin: that is, whether a given basement membrane laminin is contributed by epithelium, mesenchyme, or both. Our findings reveal major differences in basement composition along the body axis, with the rostral neural tube (at mandibular arch and heart levels) exhibiting many distinct laminin variants, while the lumbar level where the neural tube is just closing shows a much simpler laminin profile. Moreover, there appears to be a marked difference in the extent to which the mesenchyme contributes laminin variants to the basement membrane, with potential contribution of several laminins rostrally, but no contribution caudally. This information paves the way towards a mechanistic analysis of basement membrane laminin function during early neural tube development in mammals. PMID:21524702

Early Parenting Moderates the Association between Parental Depression and Neural Reactivity to Rewards and Losses in Offspring.

PubMed

Kujawa, Autumn; Proudfit, Greg H; Laptook, Rebecca; Klein, Daniel N

2015-07-01

Children of parents with depression exhibit neural abnormalities in reward processing. Examining contributions of parenting could provide insight into the development of these abnormalities and to the etiology of depression. We evaluated whether early parenting moderates the effects of parental depression on a neural measure of reward and loss processing in mid-late childhood. Parenting was assessed when children were preschoolers. At age nine, children completed an event-related potential assessment and the feedback negativity (FN) was measured following rewards and losses ( N =344). Maternal authoritative parenting moderated the effect of maternal depression; among offspring of mothers with histories of depression, low authoritative parenting predicted a blunted FN. Observed maternal positive parenting interacted with paternal depression in a comparable manner, indicating that maternal parenting may buffer the effects of paternal depression. Early parenting may be important in shaping the neural systems involved in reward processing among children at high risk for depression.

Early Parenting Moderates the Association between Parental Depression and Neural Reactivity to Rewards and Losses in Offspring

PubMed Central

Kujawa, Autumn; Proudfit, Greg H.; Laptook, Rebecca; Klein, Daniel N.

2014-01-01

Children of parents with depression exhibit neural abnormalities in reward processing. Examining contributions of parenting could provide insight into the development of these abnormalities and to the etiology of depression. We evaluated whether early parenting moderates the effects of parental depression on a neural measure of reward and loss processing in mid-late childhood. Parenting was assessed when children were preschoolers. At age nine, children completed an event-related potential assessment and the feedback negativity (FN) was measured following rewards and losses (N=344). Maternal authoritative parenting moderated the effect of maternal depression; among offspring of mothers with histories of depression, low authoritative parenting predicted a blunted FN. Observed maternal positive parenting interacted with paternal depression in a comparable manner, indicating that maternal parenting may buffer the effects of paternal depression. Early parenting may be important in shaping the neural systems involved in reward processing among children at high risk for depression. PMID:26167423

Connecting Teratogen-Induced Congenital Heart Defects to Neural Crest Cells and Their Effect on Cardiac Function

PubMed Central

Karunamuni, Ganga H.; Ma, Pei; Gu, Shi; Rollins, Andrew M.; Jenkins, Michael W.; Watanabe, Michiko

2014-01-01

Neural crest cells play many key roles in embryonic development, as demonstrated by the abnormalities that result from their specific absence or dysfunction. Unfortunately, these key cells are particularly sensitive to abnormalities in various intrinsic and extrinsic factors, such as genetic deletions or ethanol-exposure that lead to morbidity and mortality for organisms. This review discusses the role identified for a segment of neural crest is in regulating the morphogenesis of the heart and associated great vessels. The paradox is that their derivatives constitute a small proportion of cells to the cardiovascular system. Findings supporting that these cells impact early cardiac function raises the interesting possibility that they indirectly control cardiovascular development at least partially through regulating function. Making connections between insults to the neural crest, cardiac function, and morphogenesis is more approachable with technological advances. Expanding our understanding of early functional consequences could be useful in improving diagnosis and testing therapies. PMID:25220155

Self-organization of neural tissue architectures from pluripotent stem cells.

PubMed

Karus, Michael; Blaess, Sandra; Brüstle, Oliver

2014-08-15

Despite being a subject of intensive research, the mechanisms underlying the formation of neural tissue architectures during development of the central nervous system remain largely enigmatic. So far, studies into neural pattern formation have been restricted mainly to animal experiments. With the advent of pluripotent stem cells it has become possible to explore early steps of nervous system development in vitro. These studies have unraveled a remarkable propensity of primitive neural cells to self-organize into primitive patterns such as neural tube-like rosettes in vitro. Data from more advanced 3D culture systems indicate that this intrinsic propensity for self-organization can even extend to the formation of complex architectures such as a multilayered cortical neuroepithelium or an entire optic cup. These novel experimental paradigms not only demonstrate the enormous self-organization capacity of neural stem cells, they also provide exciting prospects for studying the earliest steps of human neural tissue development and the pathogenesis of brain malformations in reductionist in vitro paradigms. © 2014 Wiley Periodicals, Inc.

A Failure of Left Temporal Cortex to Specialize for Language Is an Early Emerging and Fundamental Property of Autism

ERIC Educational Resources Information Center

Eyler, Lisa T.; Pierce, Karen; Courchesne, Eric

2012-01-01

Failure to develop normal language comprehension is an early warning sign of autism, but the neural mechanisms underlying this signature deficit are unknown. This is because of an almost complete absence of functional studies of the autistic brain during early development. Using functional magnetic resonance imaging, we previously observed a trend…

Developing neuronal networks: Self-organized criticality predicts the future

NASA Astrophysics Data System (ADS)

Pu, Jiangbo; Gong, Hui; Li, Xiangning; Luo, Qingming

2013-01-01

Self-organized criticality emerged in neural activity is one of the key concepts to describe the formation and the function of developing neuronal networks. The relationship between critical dynamics and neural development is both theoretically and experimentally appealing. However, whereas it is well-known that cortical networks exhibit a rich repertoire of activity patterns at different stages during in vitro maturation, dynamical activity patterns through the entire neural development still remains unclear. Here we show that a series of metastable network states emerged in the developing and ``aging'' process of hippocampal networks cultured from dissociated rat neurons. The unidirectional sequence of state transitions could be only observed in networks showing power-law scaling of distributed neuronal avalanches. Our data suggest that self-organized criticality may guide spontaneous activity into a sequential succession of homeostatically-regulated transient patterns during development, which may help to predict the tendency of neural development at early ages in the future.

Effect of Socioeconomic Status (SES) Disparity on Neural Development in Female African-American Infants at Age 1 Month

ERIC Educational Resources Information Center

Betancourt, Laura M.; Avants, Brian; Farah, Martha J.; Brodsky, Nancy L.; Wu, Jue; Ashtari, Manzar; Hurt, Hallam

2016-01-01

There is increasing interest in both the cumulative and long-term impact of early life adversity on brain structure and function, especially as the brain is both highly vulnerable and highly adaptive during childhood. Relationships between SES and neural development have been shown in children older than age 2 years. Less is known regarding the…

EZ spheres: a stable and expandable culture system for the generation of pre-rosette multipotent stem cells from human ESCs and iPSCs.

PubMed

Ebert, Allison D; Shelley, Brandon C; Hurley, Amanda M; Onorati, Marco; Castiglioni, Valentina; Patitucci, Teresa N; Svendsen, Soshana P; Mattis, Virginia B; McGivern, Jered V; Schwab, Andrew J; Sareen, Dhruv; Kim, Ho Won; Cattaneo, Elena; Svendsen, Clive N

2013-05-01

We have developed a simple method to generate and expand multipotent, self-renewing pre-rosette neural stem cells from both human embryonic stem cells (hESCs) and human induced pluripotent stem cells (iPSCs) without utilizing embryoid body formation, manual selection techniques, or complex combinations of small molecules. Human ESC and iPSC colonies were lifted and placed in a neural stem cell medium containing high concentrations of EGF and FGF-2. Cell aggregates (termed EZ spheres) could be expanded for long periods using a chopping method that maintained cell-cell contact. Early passage EZ spheres rapidly down-regulated OCT4 and up-regulated SOX2 and nestin expression. They retained the potential to form neural rosettes and consistently differentiated into a range of central and peripheral neural lineages. Thus, they represent a very early neural stem cell with greater differentiation flexibility than other previously described methods. As such, they will be useful for the rapidly expanding field of neurological development and disease modeling, high-content screening, and regenerative therapies based on pluripotent stem cell technology. Copyright © 2013 Elsevier B.V. All rights reserved.

The lamprey: a jawless vertebrate model system for examining origin of the neural crest and other vertebrate traits.

PubMed

Green, Stephen A; Bronner, Marianne E

2014-01-01

Lampreys are a group of jawless fishes that serve as an important point of comparison for studies of vertebrate evolution. Lampreys and hagfishes are agnathan fishes, the cyclostomes, which sit at a crucial phylogenetic position as the only living sister group of the jawed vertebrates. Comparisons between cyclostomes and jawed vertebrates can help identify shared derived (i.e. synapomorphic) traits that might have been inherited from ancestral early vertebrates, if unlikely to have arisen convergently by chance. One example of a uniquely vertebrate trait is the neural crest, an embryonic tissue that produces many cell types crucial to vertebrate features, such as the craniofacial skeleton, pigmentation of the skin, and much of the peripheral nervous system (Gans and Northcutt, 1983). Invertebrate chordates arguably lack unambiguous neural crest homologs, yet have cells with some similarities, making comparisons with lampreys and jawed vertebrates essential for inferring characteristics of development in early vertebrates, and how they may have evolved from nonvertebrate chordates. Here we review recent research on cyclostome neural crest development, including research on lamprey gene regulatory networks and differentiated neural crest fates. Copyright © 2014 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

Robo signaling regulates the production of cranial neural crest cells.

PubMed

Li, Yan; Zhang, Xiao-Tan; Wang, Xiao-Yu; Wang, Guang; Chuai, Manli; Münsterberg, Andrea; Yang, Xuesong

2017-12-01

Slit/Robo signaling plays an important role in the guidance of developing neurons in developing embryos. However, it remains obscure whether and how Slit/Robo signaling is involved in the production of cranial neural crest cells. In this study, we examined Robo1 deficient mice to reveal developmental defects of mouse cranial frontal and parietal bones, which are derivatives of cranial neural crest cells. Therefore, we determined the production of HNK1 + cranial neural crest cells in early chick embryo development after knock-down (KD) of Robo1 expression. Detection of markers for pre-migratory and migratory neural crest cells, PAX7 and AP-2α, showed that production of both was affected by Robo1 KD. In addition, we found that the transcription factor slug is responsible for the aberrant delamination/EMT of cranial neural crest cells induced by Robo1 KD, which also led to elevated expression of E- and N-Cadherin. N-Cadherin expression was enhanced when blocking FGF signaling with dominant-negative FGFR1 in half of the neural tube. Taken together, we show that Slit/Robo signaling influences the delamination/EMT of cranial neural crest cells, which is required for cranial bone development. Copyright © 2017. Published by Elsevier Inc.

The Ca2+-induced methyltransferase xPRMT1b controls neural fate in amphibian embryo.

PubMed

Batut, Julie; Vandel, Laurence; Leclerc, Catherine; Daguzan, Christiane; Moreau, Marc; Néant, Isabelle

2005-10-18

We have previously shown that an increase in intracellular Ca2+ is both necessary and sufficient to commit ectoderm to a neural fate in Xenopus embryos. However, the relationship between this Ca2+ increase and the expression of early neural genes has yet to be defined. Using a subtractive cDNA library between untreated and caffeine-treated animal caps, i.e., control ectoderm and ectoderm induced toward a neural fate by a release of Ca2+, we have isolated the arginine N-methyltransferase, xPRMT1b, a Ca2+-induced target gene, which plays a pivotal role in this process. First, we show in embryo and in animal cap that xPRMT1b expression is Ca2+-regulated. Second, overexpression of xPRMT1b induces the expression of early neural genes such as Zic3. Finally, in the whole embryo, antisense approach with morpholino oligonucleotide against xPRMT1b impairs neural development and in animal caps blocks the expression of neural markers induced by a release of internal Ca2+. Our results implicate an instructive role of an enzyme, an arginine methyltransferase protein, in the embryonic choice of determination between epidermal and neural fate. The results presented provide insights by which a Ca2+ increase induces neural fate.

Using cross-species comparisons and a neurobiological framework to understand early social deprivation effects on behavioral development.

PubMed

Brett, Zoë H; Humphreys, Kathryn L; Fleming, Alison S; Kraemer, Gary W; Drury, Stacy S

2015-05-01

Building upon the transactional model of brain development, we explore the impact of early maternal deprivation on neural development and plasticity in three neural systems: hyperactivity/impulsivity, executive function, and hypothalamic-pituitary-adrenal axis functioning across rodent, nonhuman primate, and human studies. Recognizing the complexity of early maternal-infant interactions, we limit our cross-species comparisons to data from rodent models of artificial rearing, nonhuman primate studies of peer rearing, and the relations between these two experimental approaches and human studies of children exposed to the early severe psychosocial deprivation associated with institutional care. In addition to discussing the strengths and limitations of these paradigms, we present the current state of research on the neurobiological impact of early maternal deprivation and the evidence of sensitive periods, noting methodological challenges. Integrating data across preclinical animal models and human studies, we speculate about the underlying biological mechanisms; the differential impact of deprivation due to temporal factors including onset, offset, and duration of the exposure; and the possibility and consequences of reopening of sensitive periods during adolescence.

Using cross-species comparisons and a neurobiological framework to understand early social deprivation effects on behavioral development

PubMed Central

BRETT, ZOË H.; HUMPHREYS, KATHRYN L.; FLEMING, ALISON S.; KRAEMER, GARY W.; DRURY, STACY S.

2017-01-01

Building upon the transactional model of brain development, we explore the impact of early maternal deprivation on neural development and plasticity in three neural systems: hyperactivity/impulsivity, executive function, and hypothalamic–pituitary–adrenal axis functioning across rodent, nonhuman primate, and human studies. Recognizing the complexity of early maternal–infant interactions, we limit our cross-species comparisons to data from rodent models of artificial rearing, nonhuman primate studies of peer rearing, and the relations between these two experimental approaches and human studies of children exposed to the early severe psychosocial deprivation associated with institutional care. In addition to discussing the strengths and limitations of these paradigms, we present the current state of research on the neurobiological impact of early maternal deprivation and the evidence of sensitive periods, noting methodological challenges. Integrating data across preclinical animal models and human studies, we speculate about the underlying biological mechanisms; the differential impact of deprivation due to temporal factors including onset, offset, and duration of the exposure; and the possibility and consequences of reopening of sensitive periods during adolescence. PMID:25997759

Expression analysis of Egr-1 ortholog in metamorphic brain of honeybee (Apis mellifera L.): Possible evolutionary conservation of roles of Egr in eye development in vertebrates and insects.

PubMed

Ugajin, Atsushi; Watanabe, Takayuki; Uchiyama, Hironobu; Sasaki, Tetsuhiko; Yajima, Shunsuke; Ono, Masato

2016-09-16

Specific genes quickly transcribed after extracellular stimuli without de novo protein synthesis are known as immediate early genes (IEGs) and are thought to contribute to learning and memory processes in the mature nervous system of vertebrates. A recent study revealed that the homolog of Early growth response protein-1 (Egr-1), which is one of the best-characterized vertebrate IEGs, shared similar properties as a neural activity-dependent gene in the adult brain of insects. With regard to the roles of vertebrate Egr-1 in neural development, the contribution to the development and growth of visual systems has been reported. However, in insects, the expression dynamics of the Egr-1 homologous gene during neural development remains poorly understood. Our expression analysis demonstrated that AmEgr, a honeybee homolog of Egr-1, was transiently upregulated in the developing brain during the early to mid pupal stages. In situ hybridization and 5-bromo-2'-deoxyuridine (BrdU) immunohistochemistry revealed that AmEgr was mainly expressed in post-mitotic cells in optic lobes, the primary visual center of the insect brain. These findings suggest the evolutionarily conserved role of Egr homologs in the development of visual systems in vertebrates and insects. Copyright © 2016 Elsevier Inc. All rights reserved.

An Initial Investigation of the Neural Correlates of Word Processing in Preschoolers with Specific Language Impairment

ERIC Educational Resources Information Center

Haebig, Eileen; Leonard, Laurence; Usler, Evan; Deevy, Patricia; Weber, Christine

2018-01-01

Purpose: Previous behavioral studies have found deficits in lexical--semantic abilities in children with specific language impairment (SLI), including reduced depth and breadth of word knowledge. This study explored the neural correlates of early emerging familiar word processing in preschoolers with SLI and typical development. Method: Fifteen…

Loss of Neurofilament Labeling in the Primary Visual Cortex of Monocularly Deprived Monkeys

PubMed Central

Duffy, Kevin R.; Livingstone, Margaret S.

2009-01-01

Visual experience during early life is important for the development of neural organizations that support visual function. Closing one eye (monocular deprivation) during this sensitive period can cause a reorganization of neural connections within the visual system that leaves the deprived eye functionally disconnected. We have assessed the pattern of neurofilament labeling in monocularly deprived macaque monkeys to examine the possibility that a cytoskeleton change contributes to deprivation-induced reorganization of neural connections within the primary visual cortex (V-1). Monocular deprivation for three months starting around the time of birth caused a significant loss of neurofilament labeling within deprived-eye ocular dominance columns. Three months of monocular deprivation initiated in adulthood did not produce a loss of neurofilament labeling. The evidence that neurofilament loss was found only when deprivation occurred during the sensitive period supports the notion that the loss permits restructuring of deprived-eye neural connections within the visual system. These results provide evidence that, in addition to reorganization of LGN inputs, the intrinsic circuitry of V-1 neurons is altered when monocular deprivation occurs early in development. PMID:15563721

Effect of socioeconomic status (SES) disparity on neural development in female African-American infants at age 1 month.

PubMed

Betancourt, Laura M; Avants, Brian; Farah, Martha J; Brodsky, Nancy L; Wu, Jue; Ashtari, Manzar; Hurt, Hallam

2016-11-01

There is increasing interest in both the cumulative and long-term impact of early life adversity on brain structure and function, especially as the brain is both highly vulnerable and highly adaptive during childhood. Relationships between SES and neural development have been shown in children older than age 2 years. Less is known regarding the impact of SES on neural development in children before age 2. This paper examines the effect of SES, indexed by income-to-needs (ITN) and maternal education, on cortical gray, deep gray, and white matter volumes in term, healthy, appropriate for gestational age, African-American, female infants. At 5 weeks postnatal age, unsedated infants underwent MRI (3.0T Siemens Verio scanner, 32-channel head coil). Images were segmented based on a locally constructed template. Utilizing hierarchical linear regression, SES effects on MRI volumes were examined. In this cohort of healthy African-American female infants of varying SES, lower SES was associated with smaller cortical gray and deep gray matter volumes. These SES effects on neural outcome at such a young age build on similar studies of older children, suggesting that the biological embedding of adversity may occur very early in development. © 2015 John Wiley & Sons Ltd.

Histone deacetylase 1 and 2 are essential for murine neural crest proliferation, pharyngeal arch development, and craniofacial morphogenesis.

PubMed

Milstone, Zachary J; Lawson, Grace; Trivedi, Chinmay M

2017-12-01

Craniofacial anomalies involve defective pharyngeal arch development and neural crest function. Copy number variation at 1p35, containing histone deacetylase 1 (Hdac1), or 6q21-22, containing Hdac2, are implicated in patients with craniofacial defects, suggesting an important role in guiding neural crest development. However, the roles of Hdac1 and Hdac2 within neural crest cells remain unknown. The neural crest and its derivatives express both Hdac1 and Hdac2 during early murine development. Ablation of Hdac1 and Hdac2 within murine neural crest progenitor cells cause severe hemorrhage, atrophic pharyngeal arches, defective head morphogenesis, and complete embryonic lethality. Embryos lacking Hdac1 and Hdac2 in the neural crest exhibit decreased proliferation and increased apoptosis in both the neural tube and the first pharyngeal arch. Mechanistically, loss of Hdac1 and Hdac2 upregulates cyclin-dependent kinase inhibitors Cdkn1a, Cdkn1b, Cdkn1c, Cdkn2b, Cdkn2c, and Tp53 within the first pharyngeal arch. Our results show that Hdac1 and Hdac2 function redundantly within the neural crest to regulate proliferation and the development of the pharyngeal arches by means of repression of cyclin-dependent kinase inhibitors. Developmental Dynamics 246:1015-1026, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Fgfr1 regulates patterning of the pharyngeal region

PubMed Central

Trokovic, Nina; Trokovic, Ras; Mai, Petra; Partanen, Juha

2003-01-01

Development of the pharyngeal region depends on the interaction and integration of different cell populations, including surface ectoderm, foregut endoderm, paraxial mesoderm, and neural crest. Mice homozygous for a hypomorphic allele of Fgfr1 have craniofacial defects, some of which appeared to result from a failure in the early development of the second branchial arch. A stream of neural crest cells was found to originate from the rhombomere 4 region and migrate toward the second branchial arch in the mutants. Neural crest cells mostly failed to enter the second arch, however, but accumulated in a region proximal to it. Both rescue of the hypomorphic Fgfr1 allele and inactivation of a conditional Fgfr1 allele specifically in neural crest cells indicated that Fgfr1 regulates the entry of neural crest cells into the second branchial arch non-cell-autonomously. Gene expression in the pharyngeal ectoderm overlying the developing second branchial arch was affected in the hypomorphic Fgfr1 mutants at a stage prior to neural crest entry. Our results indicate that Fgfr1 patterns the pharyngeal region to create a permissive environment for neural crest cell migration. PMID:12514106

Sox5 is a DNA binding co-factor for BMP R-Smads that directs target specificity during patterning of the early ectoderm

PubMed Central

Nordin, Kara; LaBonne, Carole

2014-01-01

SUMMARY The SoxD factor, Sox5, is expressed in ectodermal cells at times and places where BMP signaling is active, including the cells of the animal hemisphere at blastula stages, and the neural plate border (NPB) and neural crest (NC) at neurula stages. Sox5 is required for proper ectoderm development, and deficient embryos display patterning defects characteristic of perturbations of BMP signaling, including loss of neural crest and epidermis and expansion of the neural plate. We show that Sox5 is essential for activation of BMP target genes in embryos and explants, that it physically interacts with BMP R-Smads, and that it is essential for recruitment of Smad1/4 to BMP regulatory elements. Our findings identify Sox5 as the long sought DNA binding partner for BMP R-Smads essential to plasticity and pattern in the early ectoderm. PMID:25453832

Biological impact of preschool music classes on processing speech in noise

PubMed Central

Strait, Dana L.; Parbery-Clark, Alexandra; O’Connell, Samantha; Kraus, Nina

2013-01-01

Musicians have increased resilience to the effects of noise on speech perception and its neural underpinnings. We do not know, however, how early in life these enhancements arise. We compared auditory brainstem responses to speech in noise in 32 preschool children, half of whom were engaged in music training. Thirteen children returned for testing one year later, permitting the first longitudinal assessment of subcortical auditory function with music training. Results indicate emerging neural enhancements in musically trained preschoolers for processing speech in noise. Longitudinal outcomes reveal that children enrolled in music classes experience further increased neural resilience to background noise following one year of continued training compared to nonmusician peers. Together, these data reveal enhanced development of neural mechanisms undergirding speech-in-noise perception in preschoolers undergoing music training and may indicate a biological impact of music training on auditory function during early childhood. PMID:23872199

Biological impact of preschool music classes on processing speech in noise.

PubMed

Strait, Dana L; Parbery-Clark, Alexandra; O'Connell, Samantha; Kraus, Nina

2013-10-01

Musicians have increased resilience to the effects of noise on speech perception and its neural underpinnings. We do not know, however, how early in life these enhancements arise. We compared auditory brainstem responses to speech in noise in 32 preschool children, half of whom were engaged in music training. Thirteen children returned for testing one year later, permitting the first longitudinal assessment of subcortical auditory function with music training. Results indicate emerging neural enhancements in musically trained preschoolers for processing speech in noise. Longitudinal outcomes reveal that children enrolled in music classes experience further increased neural resilience to background noise following one year of continued training compared to nonmusician peers. Together, these data reveal enhanced development of neural mechanisms undergirding speech-in-noise perception in preschoolers undergoing music training and may indicate a biological impact of music training on auditory function during early childhood. Copyright © 2013 Elsevier Ltd. All rights reserved.

Misexpression of BRE gene in the developing chick neural tube affects neurulation and somitogenesis

PubMed Central

Wang, Guang; Li, Yan; Wang, Xiao-Yu; Chuai, Manli; Yeuk-Hon Chan, John; Lei, Jian; Münsterberg, Andrea; Lee, Kenneth Ka Ho; Yang, Xuesong

2015-01-01

The brain and reproductive expression (BRE) gene is expressed in numerous adult tissues and especially in the nervous and reproductive systems. However, little is known about BRE expression in the developing embryo or about its role in embryonic development. In this study, we used in situ hybridization to reveal the spatiotemporal expression pattern for BRE in chick embryo during development. To determine the importance of BRE in neurogenesis, we overexpressed BRE and also silenced BRE expression specifically in the neural tube. We established that overexpressing BRE in the neural tube indirectly accelerated Pax7+ somite development and directly increased HNK-1+ neural crest cell (NCC) migration and TuJ-1+ neurite outgrowth. These altered morphogenetic processes were associated with changes in the cell cycle of NCCs and neural tube cells. The inverse effect was obtained when BRE expression was silenced in the neural tube. We also determined that BMP4 and Shh expression in the neural tube was affected by misexpression of BRE. This provides a possible mechanism for how altering BRE expression was able to affect somitogenesis, neurogenesis, and NCC migration. In summary, our results demonstrate that BRE plays an important role in regulating neurogenesis and indirectly somite differentiation during early chick embryo development. PMID:25568339

Dynamic methylation and expression of Oct4 in early neural stem cells.

PubMed

Lee, Shih-Han; Jeyapalan, Jennie N; Appleby, Vanessa; Mohamed Noor, Dzul Azri; Sottile, Virginie; Scotting, Paul J

2010-09-01

Neural stem cells are a multipotent population of tissue-specific stem cells with a broad but limited differentiation potential. However, recent studies have shown that over-expression of the pluripotency gene, Oct4, alone is sufficient to initiate a process by which these can form 'induced pluripotent stem cells' (iPS cells) with the same broad potential as embryonic stem cells. This led us to examine the expression of Oct4 in endogenous neural stem cells, as data regarding its expression in neural stem cells in vivo are contradictory and incomplete. In this study we have therefore analysed the expression of Oct4 and other genes associated with pluripotency throughout development of the mouse CNS and in neural stem cells grown in vitro. We find that Oct4 is still expressed in the CNS by E8.5, but that this expression declines rapidly until it is undetectable by E15.5. This decline is coincident with the gradual methylation of the Oct4 promoter and proximal enhancer. Immunostaining suggests that the Oct4 protein is predominantly cytoplasmic in location. We also found that neural stem cells from all ages expressed the pluripotency associated genes, Sox2, c-Myc, Klf4 and Nanog. These data provide an explanation for the varying behaviour of cells from the early neuroepithelium at different stages of development. The expression of these genes also provides an indication of why Oct4 alone is sufficient to induce iPS formation in neural stem cells at later stages.

Early visual experience and the recognition of basic facial expressions: involvement of the middle temporal and inferior frontal gyri during haptic identification by the early blind

PubMed Central

Kitada, Ryo; Okamoto, Yuko; Sasaki, Akihiro T.; Kochiyama, Takanori; Miyahara, Motohide; Lederman, Susan J.; Sadato, Norihiro

2012-01-01

Face perception is critical for social communication. Given its fundamental importance in the course of evolution, the innate neural mechanisms can anticipate the computations necessary for representing faces. However, the effect of visual deprivation on the formation of neural mechanisms that underlie face perception is largely unknown. We previously showed that sighted individuals can recognize basic facial expressions by haptics surprisingly well. Moreover, the inferior frontal gyrus (IFG) and posterior superior temporal sulcus (pSTS) in the sighted subjects are involved in haptic and visual recognition of facial expressions. Here, we conducted both psychophysical and functional magnetic-resonance imaging (fMRI) experiments to determine the nature of the neural representation that subserves the recognition of basic facial expressions in early blind individuals. In a psychophysical experiment, both early blind and sighted subjects haptically identified basic facial expressions at levels well above chance. In the subsequent fMRI experiment, both groups haptically identified facial expressions and shoe types (control). The sighted subjects then completed the same task visually. Within brain regions activated by the visual and haptic identification of facial expressions (relative to that of shoes) in the sighted group, corresponding haptic identification in the early blind activated regions in the inferior frontal and middle temporal gyri. These results suggest that the neural system that underlies the recognition of basic facial expressions develops supramodally even in the absence of early visual experience. PMID:23372547

Early visual experience and the recognition of basic facial expressions: involvement of the middle temporal and inferior frontal gyri during haptic identification by the early blind.

PubMed

Kitada, Ryo; Okamoto, Yuko; Sasaki, Akihiro T; Kochiyama, Takanori; Miyahara, Motohide; Lederman, Susan J; Sadato, Norihiro

2013-01-01

Face perception is critical for social communication. Given its fundamental importance in the course of evolution, the innate neural mechanisms can anticipate the computations necessary for representing faces. However, the effect of visual deprivation on the formation of neural mechanisms that underlie face perception is largely unknown. We previously showed that sighted individuals can recognize basic facial expressions by haptics surprisingly well. Moreover, the inferior frontal gyrus (IFG) and posterior superior temporal sulcus (pSTS) in the sighted subjects are involved in haptic and visual recognition of facial expressions. Here, we conducted both psychophysical and functional magnetic-resonance imaging (fMRI) experiments to determine the nature of the neural representation that subserves the recognition of basic facial expressions in early blind individuals. In a psychophysical experiment, both early blind and sighted subjects haptically identified basic facial expressions at levels well above chance. In the subsequent fMRI experiment, both groups haptically identified facial expressions and shoe types (control). The sighted subjects then completed the same task visually. Within brain regions activated by the visual and haptic identification of facial expressions (relative to that of shoes) in the sighted group, corresponding haptic identification in the early blind activated regions in the inferior frontal and middle temporal gyri. These results suggest that the neural system that underlies the recognition of basic facial expressions develops supramodally even in the absence of early visual experience.

The Development of Attentional Biases for Faces in Infancy: A Developmental Systems Perspective

PubMed Central

Reynolds, Greg D.; Roth, Kelly C.

2018-01-01

We present an integrative review of research and theory on major factors involved in the early development of attentional biases to faces. Research utilizing behavioral, eye-tracking, and neuroscience measures with infant participants as well as comparative research with animal subjects are reviewed. We begin with coverage of research demonstrating the presence of an attentional bias for faces shortly after birth, such as newborn infants’ visual preference for face-like over non-face stimuli. The role of experience and the process of perceptual narrowing in face processing are examined as infants begin to demonstrate enhanced behavioral and neural responsiveness to mother over stranger, female over male, own- over other-race, and native over non-native faces. Next, we cover research on developmental change in infants’ neural responsiveness to faces in multimodal contexts, such as audiovisual speech. We also explore the potential influence of arousal and attention on early perceptual preferences for faces. Lastly, the potential influence of the development of attention systems in the brain on social-cognitive processing is discussed. In conclusion, we interpret the findings under the framework of Developmental Systems Theory, emphasizing the combined and distributed influence of several factors, both internal (e.g., arousal, neural development) and external (e.g., early social experience) to the developing child, in the emergence of attentional biases that lead to enhanced responsiveness and processing of faces commonly encountered in the native environment. PMID:29541043

Analysis of NUAK1 and NUAK2 expression during early chick development reveals specific patterns in the developing head.

PubMed

Bekri, Abdelhamid; Billaud, Marc; Thélu, Jacques

2014-01-01

Several human diseases are associated with the NUAK1 and NUAK2 genes. These genes encode kinases, members of the AMPK-related kinases (ARK) gene family. Both NUAK1 and NUAK2 are known targets of the serine threonine kinase LKB1, a tumor suppressor involved in regulating cell polarity. While much is known about their functions in disease, their expression pattern in normal development has not been extensively studied. Here, we present the expression patterns for NUAK1 and NUAK2 in the chick during early-stage embryogenesis, until day 3 (Hamburger and Hamilton stage HH20). Several embryonic structures, in particular the nascent head, showed distinct expression levels. NUAK1 expression was first detected at stage HH6 in the rostral neural folds. It was then expressed (HH7-11) throughout the encephalalon, predominantly in the telencephalon and mesencephalon. NUAK1 expression was also detected in the splanchnic endoderm area at HH8-10, and in the vitellin vein derived from this area, but not in the heart. NUAK2 expression was first detected at stage HH6 in the neural folds. It was then found throughout the encephalon at stage HH20. Particular attention was paid in this study to the dorsal ectoderm at stages HH7 and HH8, where a local deficit or accumulation of NUAK2 mRNA were found to correlate with the direction of curvature of the neural plate. This is the first description of NUAK1 and NUAK2 expression patterns in the chick during early development; it reveals non-identical expression profiles for both genes in neural development.

NOGO-A induction and localization during chick brain development indicate a role disparate from neurite outgrowth inhibition

PubMed Central

Caltharp, Shelley A; Pira, Charmaine U; Mishima, Noboru; Youngdale, Erik N; McNeill, David S; Liwnicz, Boleslaw H; Oberg, Kerby C

2007-01-01

Background Nogo-A, a myelin-associated protein, inhibits neurite outgrowth and abates regeneration in the adult vertebrate central nervous system (CNS) and may play a role in maintaining neural pathways once established. However, the presence of Nogo-A during early CNS development is counterintuitive and hints at an additional role for Nogo-A beyond neurite inhibition. Results We isolated chicken NOGO-A and determined its sequence. A multiple alignment of the amino acid sequence across divergent species, identified five previously undescribed, Nogo-A specific conserved regions that may be relevant for development. NOGO gene transcripts (NOGO-A, NOGO-B and NOGO-C) were differentially expressed in the CNS during development and a second NOGO-A splice variant was identified. We further localized NOGO-A expression during key phases of CNS development by in situ hybridization. CNS-associated NOGO-A was induced coincident with neural plate formation and up-regulated by FGF in the transformation of non-neural ectoderm into neural precursors. NOGO-A expression was diffuse in the neuroectoderm during the early proliferative phase of development, and migration, but localized to large projection neurons of the optic tectum and tectal-associated nuclei during architectural differentiation, lamination and network establishment. Conclusion These data suggest Nogo-A plays a functional role in the determination of neural identity and/or differentiation and also appears to play a later role in the networking of large projection neurons during neurite formation and synaptogenesis. These data indicate that Nogo-A is a multifunctional protein with additional roles during CNS development that are disparate from its later role of neurite outgrowth inhibition in the adult CNS. PMID:17433109

Integrating Early Childhood Education in a Health Program: An Example from El Salvador

ERIC Educational Resources Information Center

Borisova, Ivelina; Coddington, Cathy

2010-01-01

The early childhood years (conception to age 8) are not only the most critical time for human growth but also for development and learning. Neurological and behavioral scientists document how inadequate stimulation and interactions can disrupt basic neural circuitry and cause long-term challenges for child's cognitive development. Yet, despite the…

Growth and splitting of neural sequences in songbird vocal development

PubMed Central

Okubo, Tatsuo S.; Mackevicius, Emily L.; Payne, Hannah L.; Lynch, Galen F.; Fee, Michale S.

2015-01-01

Neural sequences are a fundamental feature of brain dynamics underlying diverse behaviors, but the mechanisms by which they develop during learning remain unknown. Songbirds learn vocalizations composed of syllables; in adult birds, each syllable is produced by a different sequence of action potential bursts in the premotor cortical area HVC. Here we carried out recordings of large populations of HVC neurons in singing juvenile birds throughout learning to examine the emergence of neural sequences. Early in vocal development, HVC neurons begin producing rhythmic bursts, temporally locked to a ‘prototype’ syllable. Different neurons are active at different latencies relative to syllable onset to form a continuous sequence. Through development, as new syllables emerge from the prototype syllable, initially highly overlapping burst sequences become increasingly distinct. We propose a mechanistic model in which multiple neural sequences can emerge from the growth and splitting of a common precursor sequence. PMID:26618871

Expression of cardiac neural crest and heart genes isolated by modified differential display.

PubMed

Martinsen, Brad J; Groebner, Nathan J; Frasier, Allison J; Lohr, Jamie L

2003-08-01

The invasion of the cardiac neural crest (CNC) into the outflow tract (OFT) and subsequent outflow tract septation are critical events during vertebrate heart development. We have performed four modified differential display screens in the chick embryo to identify genes that may be involved in CNC, OFT, secondary heart field, and heart development. The screens included differential display of RNA isolated from three different axial segments containing premigratory cranial neural crest cells; of RNA from distal outflow tract, proximal outflow tract, and atrioventricular tissue of embryonic chick hearts; and of RNA isolated from left and right cranial tissues, including the early heart fields. These screens have resulted in the identification of the five cDNA clones presented here, which are expressed in the cardiac neural crest, outflow tract and developing heart in patterns that are unique in heart development.

Anosmin-1 is essential for neural crest and cranial placodes formation in Xenopus.

PubMed

Bae, Chang-Joon; Hong, Chang-Soo; Saint-Jeannet, Jean-Pierre

2018-01-15

During embryogenesis vertebrates develop a complex craniofacial skeleton associated with sensory organs. These structures are primarily derived from two embryonic cell populations the neural crest and cranial placodes, respectively. Neural crest cells and cranial placodes are specified through the integrated action of several families of signaling molecules, and the subsequent activation of a complex network of transcription factors. Here we describe the expression and function of Anosmin-1 (Anos1), an extracellular matrix protein, during neural crest and cranial placodes development in Xenopus laevis. Anos1 was identified as a target of Pax3 and Zic1, two transcription factors necessary and sufficient to generate neural crest and cranial placodes. Anos1 is expressed in cranial neural crest progenitors at early neurula stage and in cranial placode derivatives later in development. We show that Anos1 function is required for neural crest and sensory organs development in Xenopus, consistent with the defects observed in Kallmann syndrome patients carrying a mutation in ANOS1. These findings indicate that anos1 has a conserved function in the development of craniofacial structures, and indicate that anos1-depleted Xenopus embryos represent a useful model to analyze the pathogenesis of Kallmann syndrome. Copyright © 2017. Published by Elsevier Inc.

Recent advances in neural dust: towards a neural interface platform.

PubMed

Neely, Ryan M; Piech, David K; Santacruz, Samantha R; Maharbiz, Michel M; Carmena, Jose M

2018-06-01

The neural dust platform uses ultrasonic power and communication to enable a scalable, wireless, and batteryless system for interfacing with the nervous system. Ultrasound offers several advantages over alternative wireless approaches, including a safe method for powering and communicating with sub mm-sized devices implanted deep in tissue. Early studies demonstrated that neural dust motes could wirelessly transmit high-fidelity electrophysiological data in vivo, and that theoretically, this system could be miniaturized well below the mm-scale. Future developments are focused on further minimization of the platform, better encapsulation methods as a path towards truly chronic neural interfaces, improved delivery mechanisms, stimulation capabilities, and finally refinements to enable deployment of neural dust in the central nervous system. Copyright © 2017. Published by Elsevier Ltd.

Vascular pattern of the dentate gyrus is regulated by neural progenitors.

PubMed

Pombero, Ana; Garcia-Lopez, Raquel; Estirado, Alicia; Martinez, Salvador

2018-05-01

Neurogenesis is a vital process that begins during early embryonic development and continues until adulthood, though in the latter case, it is restricted to the subventricular zone and the subgranular zone of the dentate gyrus (DG). In particular, the DG's neurogenic properties are structurally and functionally unique, which may be related to its singular vascular pattern. Neurogenesis and angiogenesis share molecular signals and act synergistically, supporting the concept of a neurogenic niche as a functional unit between neural precursors cells and their environment, in which the blood vessels play an important role. Whereas it is well known that vascular development controls neural proliferation in the embryonary and in the adult brain, by releasing neurotrophic factors; the potential influence of neural cells on vascular components during angiogenesis is largely unknown. We have demonstrated that the reduction of neural progenitors leads to a significant impairment of vascular development. Since VEGF is a potential regulator in the neurogenesis-angiogenesis crosstalk, we were interested in assessing the possible role of this molecule in the hippocampal neurovascular development. Our results showed that VEGF is the molecule involved in the regulation of vascular development by neural progenitor cells in the DG.

The Late Positive Potential: A Neurophysiological Marker for Emotion Regulation in Children

ERIC Educational Resources Information Center

Dennis, Tracy A.; Hajcak, Greg

2009-01-01

Background: The ability to modulate emotional responses, or emotion regulation, is a key mechanism in the development of mood disruptions. Detection of a neural marker for emotion regulation thus has the potential to inform early detection and intervention for mood problems. One such neural marker may be the late positive potential (LPP), which is…

Auditory-neurophysiological responses to speech during early childhood: Effects of background noise

PubMed Central

White-Schwoch, Travis; Davies, Evan C.; Thompson, Elaine C.; Carr, Kali Woodruff; Nicol, Trent; Bradlow, Ann R.; Kraus, Nina

2015-01-01

Early childhood is a critical period of auditory learning, during which children are constantly mapping sounds to meaning. But learning rarely occurs under ideal listening conditions—children are forced to listen against a relentless din. This background noise degrades the neural coding of these critical sounds, in turn interfering with auditory learning. Despite the importance of robust and reliable auditory processing during early childhood, little is known about the neurophysiology underlying speech processing in children so young. To better understand the physiological constraints these adverse listening scenarios impose on speech sound coding during early childhood, auditory-neurophysiological responses were elicited to a consonant-vowel syllable in quiet and background noise in a cohort of typically-developing preschoolers (ages 3–5 yr). Overall, responses were degraded in noise: they were smaller, less stable across trials, slower, and there was poorer coding of spectral content and the temporal envelope. These effects were exacerbated in response to the consonant transition relative to the vowel, suggesting that the neural coding of spectrotemporally-dynamic speech features is more tenuous in noise than the coding of static features—even in children this young. Neural coding of speech temporal fine structure, however, was more resilient to the addition of background noise than coding of temporal envelope information. Taken together, these results demonstrate that noise places a neurophysiological constraint on speech processing during early childhood by causing a breakdown in neural processing of speech acoustics. These results may explain why some listeners have inordinate difficulties understanding speech in noise. Speech-elicited auditory-neurophysiological responses offer objective insight into listening skills during early childhood by reflecting the integrity of neural coding in quiet and noise; this paper documents typical response properties in this age group. These normative metrics may be useful clinically to evaluate auditory processing difficulties during early childhood. PMID:26113025

Atg7-Mediated Autophagy Is Involved in the Neural Crest Cell Generation in Chick Embryo.

PubMed

Wang, Guang; Chen, En-Ni; Liang, Chang; Liang, Jianxin; Gao, Lin-Rui; Chuai, Manli; Münsterberg, Andrea; Bao, Yongping; Cao, Liu; Yang, Xuesong

2018-04-01

Autophagy plays a very important role in numerous physiological and pathological events. However, it still remains unclear whether Atg7-induced autophagy is involved in the regulation of neural crest cell production. In this study, we found the co-location of Atg7 and Pax7 + neural crest cells in early chick embryo development. Upregulation of Atg7 with unilateral transfection of full-length Atg7 increased Pax7 + and HNK-1 + cephalic and trunk neural crest cell numbers compared to either Control-GFP transfection or opposite neural tubes, suggesting that Atg7 over-expression in neural tubes could enhance the production of neural crest cells. BMP4 in situ hybridization and p-Smad1/5/8 immunofluorescent staining demonstrated that upregulation of Atg7 in neural tubes suppressed the BMP4/Smad signaling, which is considered to promote the delamination of neural crest cells. Interestingly, upregulation of Atg7 in neural tubes could significantly accelerate cell progression into the S phase, implying that Atg7 modulates cell cycle progression. However, β-catenin expression was not significantly altered. Finally, we demonstrated that upregulation of the Atg7 gene could activate autophagy as did Atg8. We have also observed that similar phenotypes, such as more HNK-1 + neural crest cells in the unilateral Atg8 transfection side of neural tubes, and the transfection with full-length Atg8-GFP certainly promote the numbers of BrdU + neural crest cells in comparison to the GFP control. Taken together, we reveal that Atg7-induced autophagy is involved in regulating the production of neural crest cells in early chick embryos through the modification of the cell cycle.

AmphiPax3/7, an amphioxus paired box gene: insights into chordate myogenesis, neurogenesis, and the possible evolutionary precursor of definitive vertebrate neural crest.

PubMed

Holland, L Z; Schubert, M; Kozmik, Z; Holland, N D

1999-01-01

Amphioxus probably has only a single gene (AmphiPax3/7) in the Pax3/7 subfamily. Like its vertebrate homologs (Pax3 and Pax7), amphioxus AmphiPax3/7 is probably involved in specifying the axial musculature and muscularized notochord. During nervous system development, AmphiPax3/7 is first expressed in bilateral anteroposterior stripes along the edges of the neural plate. This early neural expression may be comparable to the transcription of Pax3 and Pax7 in some of the anterior neural crest cells of vertebrates. Previous studies by others and ourselves have demonstrated that several genes homologous to genetic markers for vertebrate neural crest are expressed along the neural plate-epidermis boundary in embryos of tunicates and amphioxus. Taken together, the early neural expression patterns of AmphiPax3/7 and other neural crest markers of amphioxus and tunicates suggest that cell populations that eventually gave rise to definitive vertebrate neural crest may have been present in ancestral invertebrate chordates. During later neurogenesis in amphioxus, AmphiPax3/7, like its vertebrate homologs, is expressed dorsally and dorsolaterally in the neural tube and may be involved in dorsoventral patterning. However, unlike its vertebrate homologs, AmphiPax3/7 is expressed only at the anterior end of the central nervous system instead of along much of the neuraxis; this amphioxus pattern may represent the loss of a primitive chordate character.

Infants' Mu Suppression during the Observation of Real and Mimicked Goal-Directed Actions

ERIC Educational Resources Information Center

Warreyn, Petra; Ruysschaert, Lieselot; Wiersema, Jan R.; Handl, Andrea; Pattyn, Griet; Roeyers, Herbert

2013-01-01

Since their discovery in the early 1990s, mirror neurons have been proposed to be related to many social-communicative abilities, such as imitation. However, research into the early manifestations of the putative neural mirroring system and its role in early social development is still inconclusive. In the current EEG study, mu suppression,…

Sleeper Effects

ERIC Educational Resources Information Center

Maurer, Daphne; Mondloch, Catherine J.; Lewis, Terri L.

2007-01-01

Early experience preserves and refines many capabilities that emerge prenatally. Here we describe another role that it plays--establishing the neural substrate for capabilities that emerge at a much later point in development. The evidence comes from sleeper effects: permanent deficits when early experience was absent in capabilities that normally…

Arrested development: early prefrontal lesions impair the maturation of moral judgement.

PubMed

Taber-Thomas, Bradley C; Asp, Erik W; Koenigs, Michael; Sutterer, Matthew; Anderson, Steven W; Tranel, Daniel

2014-04-01

Learning to make moral judgements based on considerations beyond self-interest is a fundamental aspect of moral development. A deficit in such learning is associated with poor socialization and criminal behaviour. The neural systems required for the acquisition and maturation of moral competency are not well understood. Here we show in a unique sample of neurological patients that focal lesions involving ventromedial prefrontal cortex, acquired during development, result in an abnormally egocentric pattern of moral judgement. In response to simple hypothetical moral scenarios, the patients were more likely than comparison participants to endorse self-interested actions that involved breaking moral rules or physically harming others in order to benefit themselves. This pattern (which we also found in subjects with psychopathy) differs from that of patients with adult-onset ventromedial prefrontal cortex lesions--the latter group showed normal rejection of egocentric rule violations. This novel contrast of patients with ventromedial prefrontal cortex lesions acquired during development versus during adulthood yields new evidence suggesting that the ventromedial prefrontal cortex is a critical neural substrate for the acquisition and maturation of moral competency that goes beyond self-interest to consider the welfare of others. Disruption to this affective neural system early in life interrupts moral development.

White spotting phenotype induced by targeted REST disruption during neural crest specification to a melanocyte cell lineage.

PubMed

Aoki, Hitomi; Hara, Akira; Kunisada, Takahiro

2015-05-01

Neural crest cells (NCCs) emerge from the dorsal region of the neural tube of vertebrate embryos and have the pluripotency to differentiate into both neuronal and non-neuronal lineages including melanocytes. Rest, also known as NRSF (neuro-restrictive silencer factor), is a regulator of neuronal development and function and suggested to be involved in the lineage specification of NCCs. However, further investigations of Rest gene functions in vivo have been hampered by the fact that Rest null mice show early embryonic lethality. To investigate the function of Rest in NCC development, we recently established NCC-specific Rest conditional knockout (CKO) mice and observed their neonatal death. Here, we have established viable heterozygous NCC-specific Rest CKO mice to analyze the function of Rest in an NCC-derived melanocyte cell lineage and found that the white spotting phenotype was associated with the reduction in the number of melanoblasts in the embryonic skin. The Rest deletion induced after the specification to melanocytes did not reduce the number of melanoblasts; therefore, the expression of REST during the early neural crest specification stage was necessary for the normal development of melanoblasts to cover all of the skin. © 2015 The Molecular Biology Society of Japan and Wiley Publishing Asia Pty Ltd.

Implications of newborn amygdala connectivity for fear and cognitive development at 6-months-of-age

PubMed Central

Graham, Alice M.; Buss, Claudia; Rasmussen, Jerod M.; Rudolph, Marc D.; Demeter, Damion V.; Gilmore, John H.; Styner, Martin; Entringer, Sonja; Wadhwa, Pathik D.; Fair, Damien A.

2015-01-01

The first year of life is an important period for emergence of fear in humans. While animal models have revealed developmental changes in amygdala circuitry accompanying emerging fear, human neural systems involved in early fear development remain poorly understood. To increase understanding of the neural foundations of human fear, it is important to consider parallel cognitive development, which may modulate associations between typical development of early fear and subsequent risk for fear-related psychopathology. We, therefore, examined amygdala functional connectivity with rs-fcMRI in 48 neonates (M=3.65 weeks, SD=1.72), and measured fear and cognitive development at 6-months-of-age. Stronger, positive neonatal amygdala connectivity to several regions, including bilateral anterior insula and ventral striatum, was prospectively associated with higher fear at 6-months. Stronger amygdala connectivity to ventral anterior cingulate/anterior medial prefrontal cortex predicted a specific phenotype of higher fear combined with more advanced cognitive development. Overall, findings demonstrate unique profiles of neonatal amygdala functional connectivity related to emerging fear and cognitive development, which may have implications for normative and pathological fear in later years. Consideration of infant fear in the context of cognitive development will likely contribute to a more nuanced understanding of fear, its neural bases, and its implications for future mental health. PMID:26499255

Automated radial basis function neural network based image classification system for diabetic retinopathy detection in retinal images

NASA Astrophysics Data System (ADS)

Anitha, J.; Vijila, C. Kezi Selva; Hemanth, D. Jude

2010-02-01

Diabetic retinopathy (DR) is a chronic eye disease for which early detection is highly essential to avoid any fatal results. Image processing of retinal images emerge as a feasible tool for this early diagnosis. Digital image processing techniques involve image classification which is a significant technique to detect the abnormality in the eye. Various automated classification systems have been developed in the recent years but most of them lack high classification accuracy. Artificial neural networks are the widely preferred artificial intelligence technique since it yields superior results in terms of classification accuracy. In this work, Radial Basis function (RBF) neural network based bi-level classification system is proposed to differentiate abnormal DR Images and normal retinal images. The results are analyzed in terms of classification accuracy, sensitivity and specificity. A comparative analysis is performed with the results of the probabilistic classifier namely Bayesian classifier to show the superior nature of neural classifier. Experimental results show promising results for the neural classifier in terms of the performance measures.

Transcriptome analysis reveals determinant stages controlling human embryonic stem cell commitment to neuronal cells.

PubMed

Li, Yuanyuan; Wang, Ran; Qiao, Nan; Peng, Guangdun; Zhang, Ke; Tang, Ke; Han, Jing-Dong J; Jing, Naihe

2017-12-01

Proper neural commitment is essential for ensuring the appropriate development of the human brain and for preventing neurodevelopmental diseases such as autism spectrum disorders, schizophrenia, and intellectual disorders. However, the molecular mechanisms underlying the neural commitment in humans remain elusive. Here, we report the establishment of a neural differentiation system based on human embryonic stem cells (hESCs) and on comprehensive RNA sequencing analysis of transcriptome dynamics during early hESC differentiation. Using weighted gene co-expression network analysis, we reveal that the hESC neurodevelopmental trajectory has five stages: pluripotency (day 0); differentiation initiation (days 2, 4, and 6); neural commitment (days 8-10); neural progenitor cell proliferation (days 12, 14, and 16); and neuronal differentiation (days 18, 20, and 22). These stages were characterized by unique module genes, which may recapitulate the early human cortical development. Moreover, a comparison of our RNA-sequencing data with several other transcriptome profiling datasets from mice and humans indicated that Module 3 associated with the day 8-10 stage is a critical window of fate switch from the pluripotency to the neural lineage. Interestingly, at this stage, no key extrinsic signals were activated. In contrast, using CRISPR/Cas9-mediated gene knockouts, we also found that intrinsic hub transcription factors, including the schizophrenia-associated SIX3 gene and septo-optic dysplasia-related HESX1 gene, are required to program hESC neural determination. Our results improve the understanding of the mechanism of neural commitment in the human brain and may help elucidate the etiology of human mental disorders and advance therapies for managing these conditions. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

The maternal brain and its plasticity in humans

PubMed Central

Kim, Pilyoung; Strathearn, Lane; Swain, James E.

2015-01-01

Early mother-infant relationships play important roles in infants’ optimal development. New mothers undergo neurobiological changes that support developing mother-infant relationships regardless of great individual differences in those relationships. In this article, we review the neural plasticity in human mothers’ brains based on functional magnetic resonance imaging (fMRI) studies. First, we review the neural circuits that are involved in establishing and maintaining mother-infant relationships. Second, we discuss early postpartum factors (e.g., birth and feeding methods, hormones, and parental sensitivity) that are associated with individual differences in maternal brain neuroplasticity. Third, we discuss abnormal changes in the maternal brain related to psychopathology (i.e., postpartum depression, posttraumatic stress disorder, substance abuse) and potential brain remodeling associated with interventions. Last, we highlight potentially important future research directions to better understand normative changes in the maternal brain and risks for abnormal changes that may disrupt early mother-infant relationships. PMID:26268151

Dynamic methylation and expression of Oct4 in early neural stem cells

PubMed Central

Lee, Shih-Han; Jeyapalan, Jennie N; Appleby, Vanessa; Mohamed Noor, Dzul Azri; Sottile, Virginie; Scotting, Paul J

2010-01-01

Neural stem cells are a multipotent population of tissue-specific stem cells with a broad but limited differentiation potential. However, recent studies have shown that over-expression of the pluripotency gene, Oct4, alone is sufficient to initiate a process by which these can form ‘induced pluripotent stem cells’ (iPS cells) with the same broad potential as embryonic stem cells. This led us to examine the expression of Oct4 in endogenous neural stem cells, as data regarding its expression in neural stem cells in vivo are contradictory and incomplete. In this study we have therefore analysed the expression of Oct4 and other genes associated with pluripotency throughout development of the mouse CNS and in neural stem cells grown in vitro. We find that Oct4 is still expressed in the CNS by E8.5, but that this expression declines rapidly until it is undetectable by E15.5. This decline is coincident with the gradual methylation of the Oct4 promoter and proximal enhancer. Immunostaining suggests that the Oct4 protein is predominantly cytoplasmic in location. We also found that neural stem cells from all ages expressed the pluripotency associated genes, Sox2, c-Myc, Klf4 and Nanog. These data provide an explanation for the varying behaviour of cells from the early neuroepithelium at different stages of development. The expression of these genes also provides an indication of why Oct4 alone is sufficient to induce iPS formation in neural stem cells at later stages. PMID:20646110

White matter maturation profiles through early childhood predict general cognitive ability.

PubMed

Deoni, Sean C L; O'Muircheartaigh, Jonathan; Elison, Jed T; Walker, Lindsay; Doernberg, Ellen; Waskiewicz, Nicole; Dirks, Holly; Piryatinsky, Irene; Dean, Doug C; Jumbe, N L

2016-03-01

Infancy and early childhood are periods of rapid brain development, during which brain structure and function mature alongside evolving cognitive ability. An important neurodevelopmental process during this postnatal period is the maturation of the myelinated white matter, which facilitates rapid communication across neural systems and networks. Though prior brain imaging studies in children (4 years of age and above), adolescents, and adults have consistently linked white matter development with cognitive maturation and intelligence, few studies have examined how these processes are related throughout early development (birth to 4 years of age). Here, we show that the profile of white matter myelination across the first 5 years of life is strongly and specifically related to cognitive ability. Using a longitudinal design, coupled with advanced magnetic resonance imaging, we demonstrate that children with above-average ability show differential trajectories of myelin development compared to average and below average ability children, even when controlling for socioeconomic status, gestation, and birth weight. Specifically, higher ability children exhibit slower but more prolonged early development, resulting in overall increased myelin measures by ~3 years of age. These results provide new insight into the early neuroanatomical correlates of cognitive ability, and suggest an early period of prolonged maturation with associated protracted white matter plasticity may result in strengthened neural networks that can better support later development. Further, these results reinforce the necessity of a longitudinal perspective in investigating typical or suspected atypical cognitive maturation.

A Two-Hit Model of Autism: Adolescence as the Second Hit

PubMed Central

Picci, Giorgia; Scherf, K. Suzanne

2015-01-01

Adolescence brings dramatic changes in behavior and neural organization. Unfortunately, for some 30% of individuals with autism, there is marked decline in adaptive functioning during adolescence. We propose a two-hit model of autism. First, early perturbations in neural development function as a “first hit” that sets up a neural system that is “built to fail” in the face of a second hit. Second, the confluence of pubertal hormones, neural reorganization, and increasing social demands during adolescence provides the “second hit” that interferes with the ability to transition into adult social roles and levels of adaptive functioning. In support of this model, we review evidence about adolescent-specific neural and behavioral development in autism. We conclude with predictions and recommendations for empirical investigation about several domains in which developmental trajectories for individuals with autism may be uniquely deterred in adolescence. PMID:26609500

The science of neural interface systems.

PubMed

Hatsopoulos, Nicholas G; Donoghue, John P

2009-01-01

The ultimate goal of neural interface research is to create links between the nervous system and the outside world either by stimulating or by recording from neural tissue to treat or assist people with sensory, motor, or other disabilities of neural function. Although electrical stimulation systems have already reached widespread clinical application, neural interfaces that record neural signals to decipher movement intentions are only now beginning to develop into clinically viable systems to help paralyzed people. We begin by reviewing state-of-the-art research and early-stage clinical recording systems and focus on systems that record single-unit action potentials. We then address the potential for neural interface research to enhance basic scientific understanding of brain function by offering unique insights in neural coding and representation, plasticity, brain-behavior relations, and the neurobiology of disease. Finally, we discuss technical and scientific challenges faced by these systems before they are widely adopted by severely motor-disabled patients.

Making an Effort to Feel Positive: Insecure Attachment in Infancy Predicts the Neural Underpinnings of Emotion Regulation in Adulthood

ERIC Educational Resources Information Center

Moutsiana, Christina; Fearon, Pasco; Murray, Lynne; Cooper, Peter; Goodyer, Ian; Johnstone, Tom; Halligan, Sarah

2014-01-01

Background: Animal research indicates that the neural substrates of emotion regulation may be persistently altered by early environmental exposures. If similar processes operate in human development then this is significant, as the capacity to regulate emotional states is fundamental to human adaptation. Methods: We utilised a 22-year longitudinal…

Ablation of proliferating neural stem cells during early life is sufficient to reduce adult hippocampal neurogenesis.

PubMed

Youssef, Mary; Krish, Varsha S; Kirshenbaum, Greer S; Atsak, Piray; Lass, Tamara J; Lieberman, Sophie R; Leonardo, E David; Dranovsky, Alex

2018-05-09

Environmental exposures during early life, but not during adolescence or adulthood, lead to persistent reductions in neurogenesis in the adult hippocampal dentate gyrus (DG). The mechanisms by which early life exposures lead to long-term deficits in neurogenesis remain unclear. Here, we investigated whether targeted ablation of dividing neural stem cells during early life is sufficient to produce long-term decreases in DG neurogenesis. Having previously found that the stem cell lineage is resistant to long-term effects of transient ablation of dividing stem cells during adolescence or adulthood (Kirshenbaum et al., 2014), we used a similar pharmacogenetic approach to target dividing neural stem cells for elimination during early life periods sensitive to environmental insults. We then assessed the Nestin stem cell lineage in adulthood. We found that the adult neural stem cell reservoir was depleted following ablation during the first postnatal week, when stem cells were highly proliferative, but not during the third postnatal week, when stem cells were more quiescent. Remarkably, ablating proliferating stem cells during either the first or third postnatal week led to reduced adult neurogenesis out of proportion to the changes in the stem cell pool, indicating a disruption of the stem cell function or niche following stem cell ablation in early life. These results highlight the first three postnatal weeks as a series of sensitive periods during which elimination of dividing stem cells leads to lasting alterations in adult DG neurogenesis and stem cell function. These findings contribute to our understanding of the relationship between DG development and adult neurogenesis, as well as suggest a possible mechanism by which early life experiences may lead to lasting deficits in adult hippocampal neurogenesis. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

The cellular basis of the convergence and extension of the Xenopus neural plate.

PubMed

Keller, R; Shih, J; Sater, A

1992-03-01

There is great interest in the patterning and morphogenesis of the vertebrate nervous system, but the morphogenetic movements involved in early neural development and their underlying cellular mechanisms are poorly understood. This paper describes the cellular basis of the early neural morphogenesis of Xenopus laevis. The results have important implications for neural induction. Mapping the fate map of the midneurula (Eagleson and Harris: J. Neurobiol. 21:427-440, 1990) back to the early gastrula with time-lapse video recording demonstrates that the prospective hindbrain and spinal cord are initially very wide and very short, and thus at the beginning of gastrulation all their precursor cells lie within a few cell diameters of the inducing mesoderm. In the midgastrula, the prospective hindbrain and spinal cord undergo very strong convergence and extension movements in two phases: In the first phase they primarily undergo thinning in the radial direction and lengthening (extension) in the animal-vegetal direction, and the second phase is characterized primarily by mediolateral narrowing (convergence) and anterior-posterior lengthening (extension). These movements also occur in sandwich explants of the gastrula, thus demonstrating the local autonomy of the forces producing them. Tracing cell movements with fluorescein dextran-labeled cells in embryos or explants shows that the initial thinning and extension occurs by radial intercalation of deep cells to form fewer layers of greater area, all of which is expressed as increased length. The subsequent convergence and extension occurs by mediolateral intercalation of deep cells to form a longer, narrower array. These results establish that a similar if not identical sequence of radial and mediolateral cell intercalations underlie convergence and extension of the neural and the mesoderm tissues (Wilson and Keller: Development, 112:289-300, 1991). Moreover, these results establish that radial and mediolateral intercalation are the principal neural cell behaviors induced by the planar signals emanating from the dorsal involuting marginal zone (the Spemann organizer) in the early gastrula (Keller et al: Develop. Dynamics, 193: 218-234, 1992). Radial and mediolateral intercalation are induced among the 5 to 7 rows of cells comprising the prospective hindbrain and spinal cord, thus producing the massive convergence and extension movements that narrow and elongate these regions of the nervous system in the late gastrula. A more general significance of these results is that neural induction is best analyzed and understood in terms of the dynamics of the morphogenetic processes involved.

Mammalian brain development and our grandmothering life history.

PubMed

Hawkes, Kristen; Finlay, Barbara L

2018-05-02

Among mammals, including humans, adult brain size and the relative size of brain components depend precisely on the duration of a highly regular process of neural development. Much wider variation is seen in rates of body growth and the state of neural maturation at life history events like birth and weaning. Large brains result from slow maturation, which in humans is accompanied by weaning early with respect to both neural maturation and longevity. The grandmother hypothesis proposes this distinctive combination of life history features evolved as ancestral populations began to depend on foods that just weaned juveniles couldn't handle. Here we trace possible reciprocal connections between brain development and life history, highlighting the resulting extended neural plasticity in a wider cognitive ecology of allomaternal care that distinguishes human ontogeny with consequences for other peculiarities of our lineage. Copyright © 2018 Elsevier Inc. All rights reserved.

Development of human nervous tissue upon differentiation of embryonic stem cells in three-dimensional culture.

PubMed

Preynat-Seauve, Olivier; Suter, David M; Tirefort, Diderik; Turchi, Laurent; Virolle, Thierry; Chneiweiss, Herve; Foti, Michelangelo; Lobrinus, Johannes-Alexander; Stoppini, Luc; Feki, Anis; Dubois-Dauphin, Michel; Krause, Karl Heinz

2009-03-01

Researches on neural differentiation using embryonic stem cells (ESC) require analysis of neurogenesis in conditions mimicking physiological cellular interactions as closely as possible. In this study, we report an air-liquid interface-based culture of human ESC. This culture system allows three-dimensional cell expansion and neural differentiation in the absence of added growth factors. Over a 3-month period, a macroscopically visible, compact tissue developed. Histological coloration revealed a dense neural-like neural tissue including immature tubular structures. Electron microscopy, immunochemistry, and electrophysiological recordings demonstrated a dense network of neurons, astrocytes, and oligodendrocytes able to propagate signals. Within this tissue, tubular structures were niches of cells resembling germinal layers of human fetal brain. Indeed, the tissue contained abundant proliferating cells expressing markers of neural progenitors. Finally, the capacity to generate neural tissues on air-liquid interface differed for different ESC lines, confirming variations of their neurogenic potential. In conclusion, this study demonstrates in vitro engineering of a human neural-like tissue with an organization that bears resemblance to early developing brain. As opposed to previously described methods, this differentiation (a) allows three-dimensional organization, (b) yields dense interconnected neural tissue with structurally and functionally distinct areas, and (c) is spontaneously guided by endogenous developmental cues.

Changes in neural circuitry associated with depression at pre-clinical, pre-motor and early motor phases of Parkinson's disease.

PubMed

Borgonovo, Janina; Allende-Castro, Camilo; Laliena, Almudena; Guerrero, Néstor; Silva, Hernán; Concha, Miguel L

2017-02-01

Although Parkinson's Disease (PD) is mostly considered a motor disorder, it can present at early stages as a non-motor pathology. Among the non-motor clinical manifestations, depression shows a high prevalence and can be one of the first clinical signs to appear, even a decade before the onset of motor symptoms. Here, we review the evidence of early dysfunction in neural circuitry associated with depression in the context of PD, focusing on pre-clinical, pre-motor and early motor phases of the disease. In the pre-clinical phase, structural and functional changes in the substantia nigra, basal ganglia and limbic structures are already observed. Some of these changes are linked to motor compensation mechanisms while others correspond to pathological processes common to PD and depression and thus could underlie the appearance of depressive symptoms during the pre-motor phase. Studies of the early motor phase (less than five years post diagnosis) reveal an association between the extent of damage in different monoaminergic systems and the appearance of emotional disorders. We propose that the limbic loop of the basal ganglia and the lateral habenula play key roles in the early genesis of depression in PD. Alterations in the neural circuitry linked with emotional control might be sensitive markers of the ongoing neurodegenerative process and thus may serve to facilitate an early diagnosis of this disease. To take advantage of this, we need to improve the clinical criteria and develop biomarkers to identify depression, which could be used to determine individuals at risk to develop PD. Copyright © 2016 Elsevier Ltd. All rights reserved.

Abnormal resting-state connectivity of motor and cognitive networks in early manifest Huntington's disease.

PubMed

Wolf, R C; Sambataro, F; Vasic, N; Depping, M S; Thomann, P A; Landwehrmeyer, G B; Süssmuth, S D; Orth, M

2014-11-01

Functional magnetic resonance imaging (fMRI) of multiple neural networks during the brain's 'resting state' could facilitate biomarker development in patients with Huntington's disease (HD) and may provide new insights into the relationship between neural dysfunction and clinical symptoms. To date, however, very few studies have examined the functional integrity of multiple resting state networks (RSNs) in manifest HD, and even less is known about whether concomitant brain atrophy affects neural activity in patients. Using MRI, we investigated brain structure and RSN function in patients with early HD (n = 20) and healthy controls (n = 20). For resting-state fMRI data a group-independent component analysis identified spatiotemporally distinct patterns of motor and prefrontal RSNs of interest. We used voxel-based morphometry to assess regional brain atrophy, and 'biological parametric mapping' analyses to investigate the impact of atrophy on neural activity. Compared with controls, patients showed connectivity changes within distinct neural systems including lateral prefrontal, supplementary motor, thalamic, cingulate, temporal and parietal regions. In patients, supplementary motor area and cingulate cortex connectivity indices were associated with measures of motor function, whereas lateral prefrontal connectivity was associated with cognition. This study provides evidence for aberrant connectivity of RSNs associated with motor function and cognition in early manifest HD when controlling for brain atrophy. This suggests clinically relevant changes of RSN activity in the presence of HD-associated cortical and subcortical structural abnormalities.

Girls' challenging social experiences in early adolescence predict neural response to rewards and depressive symptoms.

PubMed

Casement, Melynda D; Guyer, Amanda E; Hipwell, Alison E; McAloon, Rose L; Hoffmann, Amy M; Keenan, Kathryn E; Forbes, Erika E

2014-04-01

Developmental models of psychopathology posit that exposure to social stressors may confer risk for depression in adolescent girls by disrupting neural reward circuitry. The current study tested this hypothesis by examining the relationship between early adolescent social stressors and later neural reward processing and depressive symptoms. Participants were 120 girls from an ongoing longitudinal study of precursors to depression across adolescent development. Low parental warmth, peer victimization, and depressive symptoms were assessed when the girls were 11 and 12 years old, and participants completed a monetary reward guessing fMRI task and assessment of depressive symptoms at age 16. Results indicate that low parental warmth was associated with increased response to potential rewards in the medial prefrontal cortex (mPFC), striatum, and amygdala, whereas peer victimization was associated with decreased response to potential rewards in the mPFC. Furthermore, concurrent depressive symptoms were associated with increased reward anticipation response in mPFC and striatal regions that were also associated with early adolescent psychosocial stressors, with mPFC and striatal response mediating the association between social stressors and depressive symptoms. These findings are consistent with developmental models that emphasize the adverse impact of early psychosocial stressors on neural reward processing and risk for depression in adolescence. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Elevated Amygdala Response to Faces following Early Deprivation

ERIC Educational Resources Information Center

Tottenham, N.; Hare, T. A.; Millner, A.; Gilhooly, T.; Zevin, J. D.; Casey, B. J.

2011-01-01

A functional neuroimaging study examined the long-term neural correlates of early adverse rearing conditions in humans as they relate to socio-emotional development. Previously institutionalized (PI) children and a same-aged comparison group were scanned using functional magnetic resonance imaging (fMRI) while performing an Emotional Face Go/Nogo…

Modulation of Reward-Related Neural Activation on Sensation Seeking across Development

PubMed Central

Hawes, Samuel W.; Chahal, Rajpreet; Hallquist, Michael N.; Paulsen, David J.; Geier, Charles F.; Luna, Beatriz

2017-01-01

Sensation seeking is a personality construct associated with an increased propensity for engaging in risk-taking. Associations with deleterious outcomes ranging from mental health impairments to increased mortality rates highlight important public health concerns related to this construct. Although some have suggested that increased neural responsivity to reward within the ventral striatum (e.g., nucleus accumbens) may drive sensation seeking behaviors, few studies have examined the neural mechanisms associated with stable individual differences in sensation seeking across development. To address this issue, the current study used functional magnetic resonance imaging to examine the association between neural responding to reward and stable patterns of sensation seeking across a three-year follow-up period among healthy adolescents and young adults (N = 139). Results indicated that during early adolescence (~ages 10–12), increased reactivity to reward within the nucleus accumbens (NAcc) was associated with lower levels of sensation seeking across a three-year follow-up. In middle adolescence (~ages 12–16), there was no evidence of a relationship between NAcc reactivity and sensation seeking. However, during the transition from late adolescence into adulthood (~ages 17–25), heightened reward-related reactivity in the NAcc was linked to increased sensation seeking. Findings suggest that the neural mechanisms underlying individual differences in trait-like levels of sensation seeking change from early to late adolescence. PMID:27956207

Neural Crossroads in the Hematopoietic Stem Cell Niche.

PubMed

Agarwala, Sobhika; Tamplin, Owen J

2018-05-29

The hematopoietic stem cell (HSC) niche supports steady-state hematopoiesis and responds to changing needs during stress and disease. The nervous system is an important regulator of the niche, and its influence is established early in development when stem cells are specified. Most research has focused on direct innervation of the niche, however recent findings show there are different modes of neural control, including globally by the central nervous system (CNS) and hormone release, locally by neural crest-derived mesenchymal stem cells, and intrinsically by hematopoietic cells that express neural receptors and neurotransmitters. Dysregulation between neural and hematopoietic systems can contribute to disease, however new therapeutic opportunities may be found among neuroregulator drugs repurposed to support hematopoiesis. Copyright © 2018 Elsevier Ltd. All rights reserved.

Deep Convolutional Neural Network-Based Early Automated Detection of Diabetic Retinopathy Using Fundus Image.

PubMed

Xu, Kele; Feng, Dawei; Mi, Haibo

2017-11-23

The automatic detection of diabetic retinopathy is of vital importance, as it is the main cause of irreversible vision loss in the working-age population in the developed world. The early detection of diabetic retinopathy occurrence can be very helpful for clinical treatment; although several different feature extraction approaches have been proposed, the classification task for retinal images is still tedious even for those trained clinicians. Recently, deep convolutional neural networks have manifested superior performance in image classification compared to previous handcrafted feature-based image classification methods. Thus, in this paper, we explored the use of deep convolutional neural network methodology for the automatic classification of diabetic retinopathy using color fundus image, and obtained an accuracy of 94.5% on our dataset, outperforming the results obtained by using classical approaches.

Neuroimaging Studies of Normal Brain Development and Their Relevance for Understanding Childhood Neuropsychiatric Disorders

ERIC Educational Resources Information Center

Marsh, Rachel; Gerber, Andrew J.; Peterson, Bradley S.

2008-01-01

Neuroimaging findings which identify normal brain development trajectories are presented. Results show that early brain development begins with the neural tube formation and ends with myelintation. How disturbances in brain development patterns are related to childhood psychiatric disorders is examined.

Visual Circuit Development Requires Patterned Activity Mediated by Retinal Acetylcholine Receptors

PubMed Central

Burbridge, Timothy J.; Xu, Hong-Ping; Ackman, James B.; Ge, Xinxin; Zhang, Yueyi; Ye, Mei-Jun; Zhou, Z. Jimmy; Xu, Jian; Contractor, Anis; Crair, Michael C.

2014-01-01

SUMMARY The elaboration of nascent synaptic connections into highly ordered neural circuits is an integral feature of the developing vertebrate nervous system. In sensory systems, patterned spontaneous activity before the onset of sensation is thought to influence this process, but this conclusion remains controversial largely due to the inherent difficulty recording neural activity in early development. Here, we describe novel genetic and pharmacological manipulations of spontaneous retinal activity, assayed in vivo, that demonstrate a causal link between retinal waves and visual circuit refinement. We also report a de-coupling of downstream activity in retinorecipient regions of the developing brain after retinal wave disruption. Significantly, we show that the spatiotemporal characteristics of retinal waves affect the development of specific visual circuits. These results conclusively establish retinal waves as necessary and instructive for circuit refinement in the developing nervous system and reveal how neural circuits adjust to altered patterns of activity prior to experience. PMID:25466916

Early deprivation, atypical brain development, and internalizing symptoms in late childhood

PubMed Central

Bick, Johanna; Fox, Nathan; Zeanah, Charles; Nelson, Charles A.

2015-01-01

Children exposed to extreme early life neglect such as in institutional rearing are at heightened risk for developing depression and anxiety disorders, and internalizing problems more broadly. These outcomes are believed to be due to alterations in the development of neural circuitry that supports emotion regulation. The specific neurodevelopmental changes that contribute to these difficulties are largely unknown. This study examined whether microstructural alterations in white matter pathways predicted long term risk for internalizing problems in institutionally reared children. Data from 69 children were drawn from the Bucharest Early Intervention Project, a randomized clinical trial of foster care for institutionally reared children. White matter was assessed using Diffusion Tensor Imaging (DTI) when children were between 8 and 10 years of age. Internalizing symptoms were assessed at the time of the MRI scan, and once children reached 12 to 14 years of age. Results indicated that neglect-associated alterations in the external capsule and corpus callosum partially explained links between institutional rearing status and internalizing symptoms in middle childhood and early adolescence. Findings shed light on neural mechanisms contributing to increased risk for emotional difficulties among children reared in adverse conditions and have implications for prevention and intervention. PMID:26384960

Neural Correlates of Motor Learning, Transfer of Learning, and Learning to Learn

PubMed Central

Seidler, Rachael D.

2009-01-01

Recent studies on the neural bases of sensorimotor adaptation demonstrate that the cerebellar and striatal thalamocortical pathways contribute to early learning. Transfer of learning involves a reduction in the contribution of early learning networks, and increased reliance on the cerebellum. The neural correlates of learning to learn remain to be determined, but likely involve enhanced functioning of general aspects of early learning. PMID:20016293

Deficits in Top-Down Sensory Prediction in Infants At Risk due to Premature Birth.

PubMed

Emberson, Lauren L; Boldin, Alex M; Riccio, Julie E; Guillet, Ronnie; Aslin, Richard N

2017-02-06

A prominent theoretical view is that the brain is inherently predictive [1, 2] and that prediction helps drive the engine of development [3, 4]. Although infants exhibit neural signatures of top-down sensory prediction [5, 6], in order to establish that prediction supports development, it must be established that deficits in early prediction abilities alter trajectories. We investigated prediction in infants born prematurely, a leading cause of neuro-cognitive impairment worldwide [7]. Prematurity, independent of medical complications, leads to developmental disturbances [8-12] and a broad range of developmental delays [13-17]. Is an alteration in early prediction abilities the common cause? Using functional near-infrared spectroscopy (fNIRS), we measured top-down sensory prediction in preterm infants (born <33 weeks gestation) before infants exhibited clinically identifiable developmental delays (6 months corrected age). Whereas preterm infants had typical neural responses to presented visual stimuli, they exhibited altered neural responses to predicted visual stimuli. Importantly, a separate behavioral control confirmed that preterm infants detect pattern violations at the same rate as full-terms, establishing selectivity of this response to top-down predictions (e.g., not in learning an audiovisual association). These findings suggest that top-down sensory prediction plays a crucial role in development and that deficits in this ability may be the reason why preterm infants experience altered developmental trajectories and are at risk for poor developmental outcomes. Moreover, this work presents an opportunity for establishing a neuro-biomarker for early identification of infants at risk and could guide early intervention regimens. Copyright © 2017 Elsevier Ltd. All rights reserved.

Assessment of the developmental totipotency of neural cells in the cerebral cortex of mouse embryo by nuclear transfer

PubMed Central

Yamazaki, Yukiko; Makino, Hatsune; Hamaguchi-Hamada, Kayoko; Hamada, Shun; Sugino, Hidehiko; Kawase, Eihachiro; Miyata, Takaki; Ogawa, Masaharu; Yanagimachi, Ryuzo; Yagi, Takeshi

2001-01-01

When neural cells were collected from the entire cerebral cortex of developing mouse fetuses (15.5–17.5 days postcoitum) and their nuclei were transferred into enucleated oocytes, 5.5% of the reconstructed oocytes developed into normal offspring. This success rate was the highest among all previous mouse cloning experiments that used somatic cells. Forty-four percent of live embryos at 10.5 days postcoitum were morphologically normal when premature and early-postmitotic neural cells from the ventricular side of the cortex were used. In contrast, the majority (95%) of embryos were morphologically abnormal (including structural abnormalities in the neural tube) when postmitotic-differentiated neurons from the pial side of the cortex were used for cloning. Whereas 4.3% of embryos cloned with ventricular-side cells developed into healthy offspring, only 0.5% of those cloned with differentiated neurons in the pial side did so. These facts seem to suggest that the nuclei of neural cells in advanced stages of differentiation had lost their developmental totipotency. The underlying mechanism for this developmental limitation could be somatic DNA rearrangements in differentiating neural cells. PMID:11698647

Early life stress accelerates behavioral and neural maturation of the hippocampus in male mice.

PubMed

Bath, K; Manzano-Nieves, G; Goodwill, H

2016-06-01

Early life stress (ELS) increases the risk for later cognitive and emotional dysfunction. ELS is known to truncate neural development through effects on suppressing cell birth, increasing cell death, and altering neuronal morphology, effects that have been associated with behavioral profiles indicative of precocious maturation. However, how earlier silencing of growth drives accelerated behavioral maturation has remained puzzling. Here, we test the novel hypothesis that, ELS drives a switch from growth to maturation to accelerate neural and behavioral development. To test this, we used a mouse model of ELS, fragmented maternal care, and a cross-sectional dense sampling approach focusing on hippocampus and measured effects of ELS on the ontogeny of behavioral development and biomarkers of neural maturation. Consistent with previous work, ELS was associated with an earlier developmental decline in expression of markers of cell proliferation (Ki-67) and differentiation (doublecortin). However, ELS also led to a precocious arrival of Parvalbumin-positive cells, led to an earlier switch in NMDA receptor subunit expression (marker of synaptic maturity), and was associated with an earlier rise in myelin basic protein expression (key component of the myelin sheath). In addition, in a contextual fear-conditioning task, ELS accelerated the timed developmental suppression of contextual fear. Together, these data provide support for the hypothesis that ELS serves to switch neurodevelopment from processes of growth to maturation and promotes accelerated development of some forms of emotional learning. Copyright © 2016 Elsevier Inc. All rights reserved.

Neural Tuning to Numerosity Relates to Perceptual Tuning in 3-6-Year-Old Children.

PubMed

Kersey, Alyssa J; Cantlon, Jessica F

2017-01-18

Neural representations of approximate numerical value, or numerosity, have been observed in the intraparietal sulcus (IPS) in monkeys and humans, including children. Using functional magnetic resonance imaging, we show that children as young as 3-4 years old exhibit neural tuning to cardinal numerosities in the IPS and that their neural responses are accounted for by a model of numerosity coding that has been used to explain neural responses in the adult IPS. We also found that the sensitivity of children's neural tuning to number in the right IPS was comparable to their numerical discrimination sensitivity observed behaviorally, outside of the scanner. Children's neural tuning curves in the right IPS were significantly sharper than in the left IPS, indicating that numerical representations are more precise and mature more rapidly in the right hemisphere than in the left. Further, we show that children's perceptual sensitivity to numerosity can be predicted by the development of their neural sensitivity to numerosity. This research provides novel evidence of developmental continuity in the neural code underlying numerical representation and demonstrates that children's neural sensitivity to numerosity is related to their cognitive development. Here we test for the existence of neural tuning to numerosity in the developing brain in the youngest sample of children tested with fMRI to date. Although previous research shows evidence of numerical distance effects in the intraparietal sulcus of the developing brain, those effects could be explained by patterns of neural activity that do not represent neural tuning to numerosity. These data provide the first robust evidence that from as early as 3-4 years of age there is developmental continuity in how the intraparietal sulcus represents the values of numerosities. Moreover, the study goes beyond previous research by examining the relation between neural tuning and perceptual tuning in children. Copyright © 2017 the authors 0270-6474/17/370512-11$15.00/0.

Hepatocyte growth factor/scatter factor-MET signaling in neural crest-derived melanocyte development.

PubMed

Kos, L; Aronzon, A; Takayama, H; Maina, F; Ponzetto, C; Merlino, G; Pavan, W

1999-02-01

The mechanisms governing development of neural crest-derived melanocytes, and how alterations in these pathways lead to hypopigmentation disorders, are not completely understood. Hepatocyte growth factor/scatter factor (HGF/SF) signaling through the tyrosine-kinase receptor, MET, is capable of promoting the proliferation, increasing the motility, and maintaining high tyrosinase activity and melanin synthesis of melanocytes in vitro. In addition, transgenic mice that ubiquitously overexpress HGF/SF demonstrate hyperpigmentation in the skin and leptomenigenes and develop melanomas. To investigate whether HGF/ SF-MET signaling is involved in the development of neural crest-derived melanocytes, transgenic embryos, ubiquitously overexpressing HGF/SF, were analyzed. In HGF/SF transgenic embryos, the distribution of melanoblasts along the characteristic migratory pathway was not affected. However, additional ectopically localized melanoblasts were also observed in the dorsal root ganglia and neural tube, as early as 11.5 days post coitus (p.c.). We utilized an in vitro neural crest culture assay to further explore the role of HGF/SF-MET signaling in neural crest development. HGF/SF added to neural crest cultures increased melanoblast number, permitted differentiation into pigmented melanocytes, promoted melanoblast survival, and could replace mast-cell growth factor/Steel factor (MGF) in explant cultures. To examine whether HGF/SF-MET signaling is required for the proper development of melanocytes, embryos with a targeted Met null mutation (Met-/-) were analysed. In Met-/- embryos, melanoblast number and location were not overtly affected up to 14 days p.c. These results demonstrate that HGF/SF-MET signaling influences, but is not required for, the initial development of neural crest-derived melanocytes in vivo and in vitro.

Human amniotic fluid contaminants alter thyroid hormone signalling and early brain development in Xenopus embryos

NASA Astrophysics Data System (ADS)

Fini, Jean-Baptiste; Mughal, Bilal B.; Le Mével, Sébastien; Leemans, Michelle; Lettmann, Mélodie; Spirhanzlova, Petra; Affaticati, Pierre; Jenett, Arnim; Demeneix, Barbara A.

2017-03-01

Thyroid hormones are essential for normal brain development in vertebrates. In humans, abnormal maternal thyroid hormone levels during early pregnancy are associated with decreased offspring IQ and modified brain structure. As numerous environmental chemicals disrupt thyroid hormone signalling, we questioned whether exposure to ubiquitous chemicals affects thyroid hormone responses during early neurogenesis. We established a mixture of 15 common chemicals at concentrations reported in human amniotic fluid. An in vivo larval reporter (GFP) assay served to determine integrated thyroid hormone transcriptional responses. Dose-dependent effects of short-term (72 h) exposure to single chemicals and the mixture were found. qPCR on dissected brains showed significant changes in thyroid hormone-related genes including receptors, deiodinases and neural differentiation markers. Further, exposure to mixture also modified neural proliferation as well as neuron and oligodendrocyte size. Finally, exposed tadpoles showed behavioural responses with dose-dependent reductions in mobility. In conclusion, exposure to a mixture of ubiquitous chemicals at concentrations found in human amniotic fluid affect thyroid hormone-dependent transcription, gene expression, brain development and behaviour in early embryogenesis. As thyroid hormone signalling is strongly conserved across vertebrates the results suggest that ubiquitous chemical mixtures could be exerting adverse effects on foetal human brain development.

Insights into Metabolic Mechanisms Underlying Folate-Responsive Neural Tube Defects: A Minireview

PubMed Central

Beaudin, Anna E.; Stover, Patrick J.

2015-01-01

Neural tube defects (NTDs), including anencephaly and spina bifida, arise from the failure of neurulation during early embryonic development. Neural tube defects are common birth defects with a heterogenous and multifactorial etiology with interacting genetic and environmental risk factors. Although the mechanisms resulting in failure of neural tube closure are unknown, up to 70% of NTDs can be prevented by maternal folic acid supplementation. However, the metabolic mechanisms underlying the association between folic acid and NTD pathogenesis have not been identified. This review summarizes our current understanding of the mechanisms by which impairments in folate metabolism might ultimately lead to failure of neural tube closure, with an emphasis on untangling the relative contributions of nutritional deficiency and genetic risk factors to NTD pathogenesis. PMID:19180567

Regulation of cell protrusions by small GTPases during fusion of the neural folds

PubMed Central

Rolo, Ana; Savery, Dawn; Escuin, Sarah; de Castro, Sandra C; Armer, Hannah EJ; Munro, Peter MG; Molè, Matteo A; Greene, Nicholas DE; Copp, Andrew J

2016-01-01

Epithelial fusion is a crucial process in embryonic development, and its failure underlies several clinically important birth defects. For example, failure of neural fold fusion during neurulation leads to open neural tube defects including spina bifida. Using mouse embryos, we show that cell protrusions emanating from the apposed neural fold tips, at the interface between the neuroepithelium and the surface ectoderm, are required for completion of neural tube closure. By genetically ablating the cytoskeletal regulators Rac1 or Cdc42 in the dorsal neuroepithelium, or in the surface ectoderm, we show that these protrusions originate from surface ectodermal cells and that Rac1 is necessary for the formation of membrane ruffles which typify late closure stages, whereas Cdc42 is required for the predominance of filopodia in early neurulation. This study provides evidence for the essential role and molecular regulation of membrane protrusions prior to fusion of a key organ primordium in mammalian development. DOI: http://dx.doi.org/10.7554/eLife.13273.001 PMID:27114066

Early print-tuned ERP response with minimal involvement of linguistic processing in Japanese Hiragana strings.

PubMed

Okumura, Yasuko; Kasai, Tetsuko; Murohashi, Harumitsu

2014-04-16

The act of reading leads to the development of specific neural responses for print, the most frequently reported of which is the left occipitotemporal N170 component of event-related potentials. However, it remains unclear whether this electrophysiological response solely involves print-tuned neural activities. The present study examined an early print-tuned event-related potential response with minimal involvement of linguistic processing in a nonalphabetic language. Japanese Hiragana words, nonwords, and alphanumeric symbol strings were presented rapidly and the task was to detect the change in color of a fixation cross to restrict linguistic processing. As a result, Hiragana words and nonwords elicited a larger posterior N1 than alphanumeric symbol strings bilaterally, irrespective of intercharacter spacing. The fact that this N1 was enhanced specifically for rapidly presented Hiragana strings suggests the existence of print-tuned neural processes that are relatively independent of the influence of linguistic processing.

Quantitative Live Imaging of Human Embryonic Stem Cell Derived Neural Rosettes Reveals Structure-Function Dynamics Coupled to Cortical Development.

PubMed

Ziv, Omer; Zaritsky, Assaf; Yaffe, Yakey; Mutukula, Naresh; Edri, Reuven; Elkabetz, Yechiel

2015-10-01

Neural stem cells (NSCs) are progenitor cells for brain development, where cellular spatial composition (cytoarchitecture) and dynamics are hypothesized to be linked to critical NSC capabilities. However, understanding cytoarchitectural dynamics of this process has been limited by the difficulty to quantitatively image brain development in vivo. Here, we study NSC dynamics within Neural Rosettes--highly organized multicellular structures derived from human pluripotent stem cells. Neural rosettes contain NSCs with strong epithelial polarity and are expected to perform apical-basal interkinetic nuclear migration (INM)--a hallmark of cortical radial glial cell development. We developed a quantitative live imaging framework to characterize INM dynamics within rosettes. We first show that the tendency of cells to follow the INM orientation--a phenomenon we referred to as radial organization, is associated with rosette size, presumably via mechanical constraints of the confining structure. Second, early forming rosettes, which are abundant with founder NSCs and correspond to the early proliferative developing cortex, show fast motions and enhanced radial organization. In contrast, later derived rosettes, which are characterized by reduced NSC capacity and elevated numbers of differentiated neurons, and thus correspond to neurogenesis mode in the developing cortex, exhibit slower motions and decreased radial organization. Third, later derived rosettes are characterized by temporal instability in INM measures, in agreement with progressive loss in rosette integrity at later developmental stages. Finally, molecular perturbations of INM by inhibition of actin or non-muscle myosin-II (NMII) reduced INM measures. Our framework enables quantification of cytoarchitecture NSC dynamics and may have implications in functional molecular studies, drug screening, and iPS cell-based platforms for disease modeling.

Early warning of illegal development for protected areas by integrating cellular automata with neural networks.

PubMed

Li, Xia; Lao, Chunhua; Liu, Yilun; Liu, Xiaoping; Chen, Yimin; Li, Shaoying; Ai, Bing; He, Zijian

2013-11-30

Ecological security has become a major issue under fast urbanization in China. As the first two cities in this country, Shenzhen and Dongguan issued the ordinance of Eco-designated Line of Control (ELC) to "wire" ecologically important areas for strict protection in 2005 and 2009 respectively. Early warning systems (EWS) are a useful tool for assisting the implementation ELC. In this study, a multi-model approach is proposed for the early warning of illegal development by integrating cellular automata (CA) and artificial neural networks (ANN). The objective is to prevent the ecological risks or catastrophe caused by such development at an early stage. The integrated model is calibrated by using the empirical information from both remote sensing and handheld GPS (global positioning systems). The MAR indicator which is the ratio of missing alarms to all the warnings is proposed for better assessment of the model performance. It is found that the fast urban development has caused significant threats to natural-area protection in the study area. The integration of CA, ANN and GPS provides a powerful tool for describing and predicting illegal development which is in highly non-linear and fragmented forms. The comparison shows that this multi-model approach has much better performances than the single-model approach for the early warning. Compared with the single models of CA and ANN, this integrated multi-model can improve the value of MAR by 65.48% and 5.17% respectively. Copyright © 2013 Elsevier Ltd. All rights reserved.

Regulation of Msx genes by a Bmp gradient is essential for neural crest specification.

PubMed

Tribulo, Celeste; Aybar, Manuel J; Nguyen, Vu H; Mullins, Mary C; Mayor, Roberto

2003-12-01

There is evidence in Xenopus and zebrafish embryos that the neural crest/neural folds are specified at the border of the neural plate by a precise threshold concentration of a Bmp gradient. In order to understand the molecular mechanism by which a gradient of Bmp is able to specify the neural crest, we analyzed how the expression of Bmp targets, the Msx genes, is regulated and the role that Msx genes has in neural crest specification. As Msx genes are directly downstream of Bmp, we analyzed Msx gene expression after experimental modification in the level of Bmp activity by grafting a bead soaked with noggin into Xenopus embryos, by expressing in the ectoderm a dominant-negative Bmp4 or Bmp receptor in Xenopus and zebrafish embryos, and also through Bmp pathway component mutants in the zebrafish. All the results show that a reduction in the level of Bmp activity leads to an increase in the expression of Msx genes in the neural plate border. Interestingly, by reaching different levels of Bmp activity in animal cap ectoderm, we show that a specific concentration of Bmp induces msx1 expression to a level similar to that required to induce neural crest. Our results indicate that an intermediate level of Bmp activity specifies the expression of Msx genes in the neural fold region. In addition, we have analyzed the role that msx1 plays on neural crest specification. As msx1 has a role in dorsoventral pattering, we have carried out conditional gain- and loss-of-function experiments using different msx1 constructs fused to a glucocorticoid receptor element to avoid an early effect of this factor. We show that msx1 expression is able to induce all other early neural crest markers tested (snail, slug, foxd3) at the time of neural crest specification. Furthermore, the expression of a dominant negative of Msx genes leads to the inhibition of all the neural crest markers analyzed. It has been previously shown that snail is one of the earliest genes acting in the neural crest genetic cascade. In order to study the hierarchical relationship between msx1 and snail/slug we performed several rescue experiments using dominant negatives for these genes. The rescuing activity by snail and slug on neural crest development of the msx1 dominant negative, together with the inability of msx1 to rescue the dominant negatives of slug and snail strongly argue that msx1 is upstream of snail and slug in the genetic cascade that specifies the neural crest in the ectoderm. We propose a model where a gradient of Bmp activity specifies the expression of Msx genes in the neural folds, and that this expression is essential for the early specification of the neural crest.

Krox20 defines a subpopulation of cardiac neural crest cells contributing to arterial valves and bicuspid aortic valve.

PubMed

Odelin, Gaëlle; Faure, Emilie; Coulpier, Fanny; Di Bonito, Maria; Bajolle, Fanny; Studer, Michèle; Avierinos, Jean-François; Charnay, Patrick; Topilko, Piotr; Zaffran, Stéphane

2018-01-03

Although cardiac neural crest cells are required at early stages of arterial valve development, their contribution during valvular leaflet maturation remains poorly understood. Here, we show in mouse that neural crest cells from pre-otic and post-otic regions make distinct contributions to the arterial valve leaflets. Genetic fate-mapping analysis of Krox20-expressing neural crest cells shows a large contribution to the borders and the interleaflet triangles of the arterial valves. Loss of Krox20 function results in hyperplastic aortic valve and partially penetrant bicuspid aortic valve formation. Similar defects are observed in neural crest Krox20 -deficient embryos. Genetic lineage tracing in Krox20 -/- mutant mice shows that endothelial-derived cells are normal, whereas neural crest-derived cells are abnormally increased in number and misplaced in the valve leaflets. In contrast, genetic ablation of Krox20 -expressing cells is not sufficient to cause an aortic valve defect, suggesting that adjacent cells can compensate this depletion. Our findings demonstrate a crucial role for Krox20 in arterial valve development and reveal that an excess of neural crest cells may be associated with bicuspid aortic valve. © 2018. Published by The Company of Biologists Ltd.

Beta-Actin Is Required for Proper Mouse Neural Crest Ontogeny

PubMed Central

Tondeleir, Davina; Noelanders, Rivka; Bakkali, Karima; Ampe, Christophe

2014-01-01

The mouse genome consists of six functional actin genes of which the expression patterns are temporally and spatially regulated during development and in the adult organism. Deletion of beta-actin in mouse is lethal during embryonic development, although there is compensatory expression of other actin isoforms. This suggests different isoform specific functions and, more in particular, an important function for beta-actin during early mammalian development. We here report a role for beta-actin during neural crest ontogeny. Although beta-actin null neural crest cells show expression of neural crest markers, less cells delaminate and their migration arrests shortly after. These phenotypes were associated with elevated apoptosis levels in neural crest cells, whereas proliferation levels were unchanged. Specifically the pre-migratory neural crest cells displayed higher levels of apoptosis, suggesting increased apoptosis in the neural tube accounts for the decreased amount of migrating neural crest cells seen in the beta-actin null embryos. These cells additionally displayed a lack of membrane bound N-cadherin and dramatic decrease in cadherin-11 expression which was more pronounced in the pre-migratory neural crest population, potentially indicating linkage between the cadherin-11 expression and apoptosis. By inhibiting ROCK ex vivo, the knockout neural crest cells regained migratory capacity and cadherin-11 expression was upregulated. We conclude that the presence of beta-actin is vital for survival, specifically of pre-migratory neural crest cells, their proper emigration from the neural tube and their subsequent migration. Furthermore, the absence of beta-actin affects cadherin-11 and N-cadherin function, which could partly be alleviated by ROCK inhibition, situating the Rho-ROCK signaling in a feedback loop with cadherin-11. PMID:24409333

Organotypic three-dimensional culture model of mesenchymal and epithelial cells to examine tissue fusion events.

EPA Science Inventory

Tissue fusion during early mammalian development requires coordination of multiple cell types, the extracellular matrix, and complex signaling pathways. Fusion events during processes including heart development, neural tube closure, and palatal fusion are dependent on signaling ...

Vestigial-like 3 is a novel Ets1 interacting partner and regulates trigeminal nerve formation and cranial neural crest migration

PubMed Central

Simon, Emilie; Thézé, Nadine; Fédou, Sandrine; Thiébaud, Pierre

2017-01-01

ABSTRACT Drosophila Vestigial is the founding member of a protein family containing a highly conserved domain, called Tondu, which mediates their interaction with members of the TEAD family of transcription factors (Scalloped in Drosophila). In Drosophila, the Vestigial/Scalloped complex controls wing development by regulating the expression of target genes through binding to MCAT sequences. In vertebrates, there are four Vestigial-like genes, the functions of which are still not well understood. Here, we describe the regulation and function of vestigial-like 3 (vgll3) during Xenopus early development. A combination of signals, including FGF8, Wnt8a, Hoxa2, Hoxb2 and retinoic acid, limits vgll3 expression to hindbrain rhombomere 2. We show that vgll3 regulates trigeminal placode and nerve formation and is required for normal neural crest development by affecting their migration and adhesion properties. At the molecular level, vgll3 is a potent activator of pax3, zic1, Wnt and FGF, which are important for brain patterning and neural crest cell formation. Vgll3 interacts in the embryo with Tead proteins but unexpectedly with Ets1, with which it is able to stimulate a MCAT driven luciferase reporter gene. Our findings highlight a critical function for vgll3 in vertebrate early development. PMID:28870996

Music and Cognitive Development: From Notes to Neural Networks

ERIC Educational Resources Information Center

Shore, Rebecca Ann

2010-01-01

This article investigates research on early childhood development and on both listening to music and participation in music activities by young children. Research is reviewed that explores possible relationships between various music-related experiences and cognitive development, from the "Mozart Effect" studies to participation in piano lessons…

Modeling Aircraft Wing Loads from Flight Data Using Neural Networks

NASA Technical Reports Server (NTRS)

Allen, Michael J.; Dibley, Ryan P.

2003-01-01

Neural networks were used to model wing bending-moment loads, torsion loads, and control surface hinge-moments of the Active Aeroelastic Wing (AAW) aircraft. Accurate loads models are required for the development of control laws designed to increase roll performance through wing twist while not exceeding load limits. Inputs to the model include aircraft rates, accelerations, and control surface positions. Neural networks were chosen to model aircraft loads because they can account for uncharacterized nonlinear effects while retaining the capability to generalize. The accuracy of the neural network models was improved by first developing linear loads models to use as starting points for network training. Neural networks were then trained with flight data for rolls, loaded reversals, wind-up-turns, and individual control surface doublets for load excitation. Generalization was improved by using gain weighting and early stopping. Results are presented for neural network loads models of four wing loads and four control surface hinge moments at Mach 0.90 and an altitude of 15,000 ft. An average model prediction error reduction of 18.6 percent was calculated for the neural network models when compared to the linear models. This paper documents the input data conditioning, input parameter selection, structure, training, and validation of the neural network models.

Gender development and the human brain.

PubMed

Hines, Melissa

2011-01-01

Convincing evidence indicates that prenatal exposure to the gonadal hormone, testosterone, influences the development of children's sex-typical toy and activity interests. In addition, growing evidence shows that testosterone exposure contributes similarly to the development of other human behaviors that show sex differences, including sexual orientation, core gender identity, and some, though not all, sex-related cognitive and personality characteristics. In addition to these prenatal hormonal influences, early infancy and puberty may provide additional critical periods when hormones influence human neurobehavioral organization. Sex-linked genes could also contribute to human gender development, and most sex-related characteristics are influenced by socialization and other aspects of postnatal experience, as well. Neural mechanisms underlying the influences of gonadal hormones on human behavior are beginning to be identified. Although the neural mechanisms underlying experiential influences remain largely uninvestigated, they could involve the same neural circuitry as that affected by hormones.

Genetics Home Reference: 3MC syndrome

MedlinePlus

... pathway is thought to help direct the movement (migration) of cells during early development before birth to ... appears to be particularly important in directing the migration of neural crest cells, which give rise to ...

From neural plate to cortical arousal-a neuronal network theory of sleep derived from in vitro "model" systems for primordial patterns of spontaneous bioelectric activity in the vertebrate central nervous system.

PubMed

Corner, Michael A

2013-05-22

In the early 1960s intrinsically generated widespread neuronal discharges were discovered to be the basis for the earliest motor behavior throughout the animal kingdom. The pattern generating system is in fact programmed into the developing nervous system, in a regionally specific manner, already at the early neural plate stage. Such rhythmically modulated phasic bursts were next discovered to be a general feature of developing neural networks and, largely on the basis of experimental interventions in cultured neural tissues, to contribute significantly to their morpho-physiological maturation. In particular, the level of spontaneous synchronized bursting is homeostatically regulated, and has the effect of constraining the development of excessive network excitability. After birth or hatching, this "slow-wave" activity pattern becomes sporadically suppressed in favor of sensory oriented "waking" behaviors better adapted to dealing with environmental contingencies. It nevertheless reappears periodically as "sleep" at several species-specific points in the diurnal/nocturnal cycle. Although this "default" behavior pattern evolves with development, its essential features are preserved throughout the life cycle, and are based upon a few simple mechanisms which can be both experimentally demonstrated and simulated by computer modeling. In contrast, a late onto- and phylogenetic aspect of sleep, viz., the intermittent "paradoxical" activation of the forebrain so as to mimic waking activity, is much less well understood as regards its contribution to brain development. Some recent findings dealing with this question by means of cholinergically induced "aroused" firing patterns in developing neocortical cell cultures, followed by quantitative electrophysiological assays of immediate and longterm sequelae, will be discussed in connection with their putative implications for sleep ontogeny.

Relationship between brainstem, cortical and behavioral measures relevant to pitch salience in humans.

PubMed

Krishnan, Ananthanarayan; Bidelman, Gavin M; Smalt, Christopher J; Ananthakrishnan, Saradha; Gandour, Jackson T

2012-10-01

Neural representation of pitch-relevant information at both the brainstem and cortical levels of processing is influenced by language or music experience. However, the functional roles of brainstem and cortical neural mechanisms in the hierarchical network for language processing, and how they drive and maintain experience-dependent reorganization are not known. In an effort to evaluate the possible interplay between these two levels of pitch processing, we introduce a novel electrophysiological approach to evaluate pitch-relevant neural activity at the brainstem and auditory cortex concurrently. Brainstem frequency-following responses and cortical pitch responses were recorded from participants in response to iterated rippled noise stimuli that varied in stimulus periodicity (pitch salience). A control condition using iterated rippled noise devoid of pitch was employed to ensure pitch specificity of the cortical pitch response. Neural data were compared with behavioral pitch discrimination thresholds. Results showed that magnitudes of neural responses increase systematically and that behavioral pitch discrimination improves with increasing stimulus periodicity, indicating more robust encoding for salient pitch. Absence of cortical pitch response in the control condition confirms that the cortical pitch response is specific to pitch. Behavioral pitch discrimination was better predicted by brainstem and cortical responses together as compared to each separately. The close correspondence between neural and behavioral data suggest that neural correlates of pitch salience that emerge in early, preattentive stages of processing in the brainstem may drive and maintain with high fidelity the early cortical representations of pitch. These neural representations together contain adequate information for the development of perceptual pitch salience. Copyright © 2012 Elsevier Ltd. All rights reserved.

Amigo adhesion protein regulates development of neural circuits in zebrafish brain.

PubMed

Zhao, Xiang; Kuja-Panula, Juha; Sundvik, Maria; Chen, Yu-Chia; Aho, Vilma; Peltola, Marjaana A; Porkka-Heiskanen, Tarja; Panula, Pertti; Rauvala, Heikki

2014-07-18

The Amigo protein family consists of three transmembrane proteins characterized by six leucine-rich repeat domains and one immunoglobulin-like domain in their extracellular moieties. Previous in vitro studies have suggested a role as homophilic adhesion molecules in brain neurons, but the in vivo functions remain unknown. Here we have cloned all three zebrafish amigos and show that amigo1 is the predominant family member expressed during nervous system development in zebrafish. Knockdown of amigo1 expression using morpholino oligonucleotides impairs the formation of fasciculated tracts in early fiber scaffolds of brain. A similar defect in fiber tract development is caused by mRNA-mediated expression of the Amigo1 ectodomain that inhibits adhesion mediated by the full-length protein. Analysis of differentiated neural circuits reveals defects in the catecholaminergic system. At the behavioral level, the disturbed formation of neural circuitry is reflected in enhanced locomotor activity and in the inability of the larvae to perform normal escape responses. We suggest that Amigo1 is essential for the development of neural circuits of zebrafish, where its mechanism involves homophilic interactions within the developing fiber tracts and regulation of the Kv2.1 potassium channel to form functional neural circuitry that controls locomotion. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Measurement of relative density of tissue using wavelet analysis and neural nets

NASA Astrophysics Data System (ADS)

Suyatinov, Sergey I.; Kolentev, Sergey V.; Buldakova, Tatyana I.

2001-01-01

Development of methods for indirect measurement of substance's consistence and characteristics is highly actual problem of medical diagnostics. Many diseases bring about changes of tissue density or appearances of alien bodies (e.g. stones in kidneys or gallbladders). Propose to use wavelet-analysis and neural nets for indirect measurement of relative density of tissue by images of internal organs. It shall allow to reveal a disease on early stage.

The SCL gene specifies haemangioblast development from early mesoderm.

PubMed

Gering, M; Rodaway, A R; Göttgens, B; Patient, R K; Green, A R

1998-07-15

The SCL gene encodes a basic helix-loop-helix (bHLH) transcription factor that is essential for the development of all haematopoietic lineages. SCL is also expressed in endothelial cells, but its function is not essential for specification of endothelial progenitors and the role of SCL in endothelial development is obscure. We isolated the zebrafish SCL homologue and show that it was co-expressed in early mesoderm with markers of haematopoietic, endothelial and pronephric progenitors. Ectopic expression of SCL mRNA in zebrafish embryos resulted in overproduction of common haematopoietic and endothelial precursors, perturbation of vasculogenesis and concomitant loss of pronephric duct and somitic tissue. Notochord and neural tube formation were unaffected. These results provide the first evidence that SCL specifies formation of haemangioblasts, the proposed common precursor of blood and endothelial lineages. Our data also underline the striking similarities between the role of SCL in haematopoiesis/vasculogenesis and the function of other bHLH proteins in muscle and neural development.

Neural Reward Processing Mediates the Relationship between Insomnia Symptoms and Depression in Adolescence

PubMed Central

Casement, Melynda D.; Keenan, Kate E.; Hipwell, Alison E.; Guyer, Amanda E.; Forbes, Erika E.

2016-01-01

Study Objectives: Emerging evidence suggests that insomnia may disrupt reward-related brain function—a potentially important factor in the development of depressive disorder. Adolescence may be a period during which such disruption is especially problematic given the rise in the incidence of insomnia and ongoing development of neural systems that support reward processing. The present study uses longitudinal data to test the hypothesis that disruption of neural reward processing is a mechanism by which insomnia symptoms—including nocturnal insomnia symptoms (NIS) and nonrestorative sleep (NRS)—contribute to depressive symptoms in adolescent girls. Method: Participants were 123 adolescent girls and their caregivers from an ongoing longitudinal study of precursors to depression across adolescent development. NIS and NRS were assessed annually from ages 9 to 13 years. Girls completed a monetary reward task during a functional MRI scan at age 16 years. Depressive symptoms were assessed at ages 16 and 17 years. Multivariable regression tested the prospective associations between NIS and NRS, neural response during reward anticipation, and the mean number of depressive symptoms (omitting sleep problems). Results: NRS, but not NIS, during early adolescence was positively associated with late adolescent dorsal medial prefrontal cortex (dmPFC) response to reward anticipation and depressive symptoms. DMPFC response mediated the relationship between early adolescent NRS and late adolescent depressive symptoms. Conclusions: These results suggest that NRS may contribute to depression by disrupting reward processing via altered activity in a region of prefrontal cortex involved in affective control. The results also support the mechanistic differentiation of NIS and NRS. Citation: Casement MD, Keenan KE, Hipwell AE, Guyer AE, Forbes EE. Neural reward processing mediates the relationship between insomnia symptoms and depression in adolescence. SLEEP 2016;39(2):439–447. PMID:26350468

Expression of polysialylated neural cell adhesion molecules on adult stem cells after neuronal differentiation of inner ear spiral ganglion neurons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, Kyoung Ho; Yeo, Sang Won, E-mail: swyeo@catholic.ac.kr; Troy, Frederic A., E-mail: fatroy@ucdavis.edu

Highlights: • PolySia expressed on neurons primarily during early stages of neuronal development. • PolySia–NCAM is expressed on neural stem cells from adult guinea pig spiral ganglion. • PolySia is a biomarker that modulates neuronal differentiation in inner ear stem cells. - Abstract: During brain development, polysialylated (polySia) neural cell adhesion molecules (polySia–NCAMs) modulate cell–cell adhesive interactions involved in synaptogenesis, neural plasticity, myelination, and neural stem cell (NSC) proliferation and differentiation. Our findings show that polySia–NCAM is expressed on NSC isolated from adult guinea pig spiral ganglion (GPSG), and in neurons and Schwann cells after differentiation of the NSC withmore » epidermal, glia, fibroblast growth factors (GFs) and neurotrophins. These differentiated cells were immunoreactive with mAb’s to polySia, NCAM, β-III tubulin, nestin, S-100 and stained with BrdU. NSC could regenerate and be differentiated into neurons and Schwann cells. We conclude: (1) polySia is expressed on NSC isolated from adult GPSG and on neurons and Schwann cells differentiated from these NSC; (2) polySia is expressed on neurons primarily during the early stage of neuronal development and is expressed on Schwann cells at points of cell–cell contact; (3) polySia is a functional biomarker that modulates neuronal differentiation in inner ear stem cells. These new findings suggest that replacement of defective cells in the inner ear of hearing impaired patients using adult spiral ganglion neurons may offer potential hope to improve the quality of life for patients with auditory dysfunction and impaired hearing disorders.« less

Establishment of turbidity forecasting model and early-warning system for source water turbidity management using back-propagation artificial neural network algorithm and probability analysis.

PubMed

Yang, Tsung-Ming; Fan, Shu-Kai; Fan, Chihhao; Hsu, Nien-Sheng

2014-08-01

The purpose of this study is to establish a turbidity forecasting model as well as an early-warning system for turbidity management using rainfall records as the input variables. The Taipei Water Source Domain was employed as the study area, and ANOVA analysis showed that the accumulative rainfall records of 1-day Ping-lin, 2-day Ping-lin, 2-day Fei-tsui, 2-day Shi-san-gu, 2-day Tai-pin and 2-day Tong-hou were the six most significant parameters for downstream turbidity development. The artificial neural network model was developed and proven capable of predicting the turbidity concentration in the investigated catchment downstream area. The observed and model-calculated turbidity data were applied to developing the turbidity early-warning system. Using a previously determined turbidity as the threshold, the rainfall criterion, above which the downstream turbidity would possibly exceed this respective threshold turbidity, for the investigated rain gauge stations was determined. An exemplary illustration demonstrated the effectiveness of the proposed turbidity early-warning system as a precautionary alarm of possible significant increase of downstream turbidity. This study is the first report of the establishment of the turbidity early-warning system. Hopefully, this system can be applied to source water turbidity forecasting during storm events and provide a useful reference for subsequent adjustment of drinking water treatment operation.

Early adversity and neural correlates of executive function: implications for academic adjustment.

PubMed

McDermott, Jennifer M; Westerlund, Alissa; Zeanah, Charles H; Nelson, Charles A; Fox, Nathan A

2012-02-15

Early adversity can negatively impact the development of cognitive functions, although little is known about whether such effects can be remediated later in life. The current study examined one facet of executive functioning - inhibitory control - among children who experienced institutional care and explored the impact of a foster care intervention within the context of the Bucharest Early Intervention Project (BEIP). Specifically, a go/nogo task was administered when children were eight years old and behavioral and event-related potential (ERP) measures were collected. Results revealed that children assigned to care as usual (i.e. institutional care) were less accurate and exhibited slower neural responses compared to children assigned to the foster care intervention and children who had never been institutionalized. However, children in both the care as usual and foster care groups exhibited diminished attention processing of nogo cues as assessed via P300 amplitude. Foster care children also showed differential reactivity between correct and error responses via the error-related negativity (ERN) as compared to children in the care as usual group. Combined, the results highlight perturbations in neural sources of behavioral and attention problems among children experiencing early adversity. Potential implications for academic adjustment in at risk children are discussed. Copyright © 2011 Elsevier Ltd. All rights reserved.

Neural Networks for Flight Control

NASA Technical Reports Server (NTRS)

Jorgensen, Charles C.

1996-01-01

Neural networks are being developed at NASA Ames Research Center to permit real-time adaptive control of time varying nonlinear systems, enhance the fault-tolerance of mission hardware, and permit online system reconfiguration. In general, the problem of controlling time varying nonlinear systems with unknown structures has not been solved. Adaptive neural control techniques show considerable promise and are being applied to technical challenges including automated docking of spacecraft, dynamic balancing of the space station centrifuge, online reconfiguration of damaged aircraft, and reducing cost of new air and spacecraft designs. Our experiences have shown that neural network algorithms solved certain problems that conventional control methods have been unable to effectively address. These include damage mitigation in nonlinear reconfiguration flight control, early performance estimation of new aircraft designs, compensation for damaged planetary mission hardware by using redundant manipulator capability, and space sensor platform stabilization. This presentation explored these developments in the context of neural network control theory. The discussion began with an overview of why neural control has proven attractive for NASA application domains. The more important issues in control system development were then discussed with references to significant technical advances in the literature. Examples of how these methods have been applied were given, followed by projections of emerging application needs and directions.

Direct brain recordings reveal impaired neural function in infants with single-suture craniosynostosis: a future modality for guiding management?

PubMed

Hashim, Peter W; Brooks, Eric D; Persing, John A; Reuman, Hannah; Naples, Adam; Travieso, Roberto; Terner, Jordan; Steinbacher, Derek; Landi, Nicole; Mayes, Linda; McPartland, James C

2015-01-01

Patients with single-suture craniosynostosis (SSC) are at an elevated risk for long-term learning disabilities. Such adverse outcomes indicate that the early development of neural processing in SSC may be abnormal. At present, however, the precise functional derangements of the developing brain remain largely unknown. Event-related potentials (ERPs) are a form of noninvasive neuroimaging that provide direct measurements of cortical activity and have shown value in predicting long-term cognitive functioning. The current study used ERPs to examine auditory processing in infants with SSC to help clarify the developmental onset of delays in this population. Fifteen infants with untreated SSC and 23 typically developing controls were evaluated. ERPs were recorded during the presentation of speech sounds. Analyses focused on the P150 and N450 components of auditory processing. Infants with SSC demonstrated attenuated P150 amplitudes relative to typically developing controls. No differences in the N450 component were identified between untreated SSC and controls. Infants with untreated SSC demonstrate abnormal speech sound processing. Atypicalities are detectable as early as 6 months of age and may represent precursors to long-term language delay. Electrophysiological assessments provide a precise examination of neural processing in SSC and hold potential as a future modality to examine the effects of surgical treatment on brain development.

Early life conditions that impact song learning in male zebra finches also impact neural and behavioral responses to song in females.

PubMed

Sewall, Kendra B; Anderson, Rindy C; Soha, Jill A; Peters, Susan; Nowicki, Stephen

2018-04-20

Early life stressors can impair song in songbirds by negatively impacting brain development and subsequent learning. Even in species in which only males sing, early life stressors might also impact female behavior and its underlying neural mechanisms, but fewer studies have examined this possibility. We manipulated brood size in zebra finches to simultaneously examine the effects of developmental stress on male song learning and female behavioral and neural response to song. Although adult male HVC volume was unaffected, we found that males from larger broods imitated tutor song less accurately. In females, early condition did not affect the direction of song preference: all females preferred tutor song over unfamiliar song in an operant test. However, treatment did affect the magnitude of behavioral response to song: females from larger broods responded less during song preference trials. This difference in activity level did not reflect boldness per se, as a separate measure of this trait did not differ with brood size. Additionally, in females we found a treatment effect on expression of the immediate early gene ZENK in response to tutor song in brain regions involved in song perception (dNCM) and social motivation (LSc.vl, BSTm, TnA), but not in a region implicated in song memory (CMM). These results are consistent with the hypothesis that developmental stressors that impair song learning in male zebra finches also influence perceptual and/or motivational processes in females. However, our results suggest that the learning of tutor song by females is robust to disturbance by developmental stress. © 2018 Wiley Periodicals, Inc. Develop Neurobiol, 2018. © 2018 Wiley Periodicals, Inc.

Neural Markers of the Development of Executive Function: Relevance for Education

PubMed Central

Shanmugan, Sheila; Satterthwaite, Theodore D.

2016-01-01

Executive functions are involved in the development of academic skills and are critical for functioning in school settings. The relevance of executive functions to education begins early and continues throughout development, with clear impact on achievement. Diverse efforts increasingly suggest ways in which facilitating development of executive function may be used to improve academic performance. Such interventions seek to alter the trajectory of executive development, which exhibits a protracted course of maturation that stretches into young adulthood. As such, it may be useful to understand how the executive system develops normally and abnormally in order to tailor interventions within educational settings. Here we review recent work investigating the neural basis for executive development during childhood and adolescence. PMID:27182537

Alteration of gene expression by alcohol exposure at early neurulation.

PubMed

Zhou, Feng C; Zhao, Qianqian; Liu, Yunlong; Goodlett, Charles R; Liang, Tiebing; McClintick, Jeanette N; Edenberg, Howard J; Li, Lang

2011-02-21

We have previously demonstrated that alcohol exposure at early neurulation induces growth retardation, neural tube abnormalities, and alteration of DNA methylation. To explore the global gene expression changes which may underline these developmental defects, microarray analyses were performed in a whole embryo mouse culture model that allows control over alcohol and embryonic variables. Alcohol caused teratogenesis in brain, heart, forelimb, and optic vesicle; a subset of the embryos also showed cranial neural tube defects. In microarray analysis (accession number GSM9545), adopting hypothesis-driven Gene Set Enrichment Analysis (GSEA) informatics and intersection analysis of two independent experiments, we found that there was a collective reduction in expression of neural specification genes (neurogenin, Sox5, Bhlhe22), neural growth factor genes [Igf1, Efemp1, Klf10 (Tieg), and Edil3], and alteration of genes involved in cell growth, apoptosis, histone variants, eye and heart development. There was also a reduction of retinol binding protein 1 (Rbp1), and de novo expression of aldehyde dehydrogenase 1B1 (Aldh1B1). Remarkably, four key hematopoiesis genes (glycophorin A, adducin 2, beta-2 microglobulin, and ceruloplasmin) were absent after alcohol treatment, and histone variant genes were reduced. The down-regulation of the neurospecification and the neurotrophic genes were further confirmed by quantitative RT-PCR. Furthermore, the gene expression profile demonstrated distinct subgroups which corresponded with two distinct alcohol-related neural tube phenotypes: an open (ALC-NTO) and a closed neural tube (ALC-NTC). Further, the epidermal growth factor signaling pathway and histone variants were specifically altered in ALC-NTO, and a greater number of neurotrophic/growth factor genes were down-regulated in the ALC-NTO than in the ALC-NTC embryos. This study revealed a set of genes vulnerable to alcohol exposure and genes that were associated with neural tube defects during early neurulation.

Generation and characterization of Tbx1-AmCyan1 transgenic reporter mouse line that selectively labels developing thymus primordium.

PubMed

Kimura, Wataru; Sharkar, Mohammad Tofael Kabir; Sultana, Nishat; Islam, Mohammod Johirul; Uezato, Tadayoshi; Miura, Naoyuki

2013-06-01

Thymus development is a complicated process that includes highly dynamic morphological changes and reciprocal tissue interactions between endoderm-derived epithelial cells of the anterior foregut and neural crest-derived mesenchymal cells. We generated and characterized a Tbx1-AmCyan1 reporter transgenic mouse to visualize thymus precursor cells during early embryonic development. In transgenic embryos, AmCyan1 fluorescence was specifically detected in the endoderm of the developing 3rd and 4th pharyngeal pouches and later in thymus epithelium until E14.5. Cells expressing AmCyan1 that were isolated based on AmCyan1 fluorescence expressed endodermal, thymic, and parathyroid markers, but they did not express neural crest or endothelial markers; these findings indicated that this transgenic mouse strain could be used to collect thymic or parathyroid precursor cells or both. We also showed that in nude mice, which exhibit defects in thymus development, the thymus precursors were clearly labeled with AmCyan1. In summary, these AmCyan1-fluorescent transgenic mice are useful for investigating early thymus development.

Neural activity during natural viewing of Sesame Street statistically predicts test scores in early childhood.

PubMed

Cantlon, Jessica F; Li, Rosa

2013-01-01

It is not currently possible to measure the real-world thought process that a child has while observing an actual school lesson. However, if it could be done, children's neural processes would presumably be predictive of what they know. Such neural measures would shed new light on children's real-world thought. Toward that goal, this study examines neural processes that are evoked naturalistically, during educational television viewing. Children and adults all watched the same Sesame Street video during functional magnetic resonance imaging (fMRI). Whole-brain intersubject correlations between the neural timeseries from each child and a group of adults were used to derive maps of "neural maturity" for children. Neural maturity in the intraparietal sulcus (IPS), a region with a known role in basic numerical cognition, predicted children's formal mathematics abilities. In contrast, neural maturity in Broca's area correlated with children's verbal abilities, consistent with prior language research. Our data show that children's neural responses while watching complex real-world stimuli predict their cognitive abilities in a content-specific manner. This more ecologically natural paradigm, combined with the novel measure of "neural maturity," provides a new method for studying real-world mathematics development in the brain.

The development of cognitive empathy and concern in preschool children: A behavioral neuroscience investigation.

PubMed

Decety, Jean; Meidenbauer, Kimberly L; Cowell, Jason M

2018-05-01

This developmental neuroscience study examined the electrophysiological responses (EEG and ERPs) associated with perspective taking and empathic concern in preschool children, as well as their relation to parental empathy dispositions and children's own prosocial behavior. Consistent with a body of previous studies using stimuli depicting somatic pain in both children and adults, larger early (~200 ms) ERPs were identified when perceiving painful versus neutral stimuli. In the slow wave window (~800 ms), a significant interaction of empathy condition and stimulus type was driven by a greater difference between painful and neutral images in the empathic concern condition. Across early development, children exhibited enhanced N2 to pain when engaging in empathic concern. Greater pain-elicited N2 responses in the cognitive empathy condition also related to parent dispositional empathy. Children's own prosocial behavior was predicted by several individual differences in neural function, including larger early LPP responses during cognitive empathy and greater differentiation in late LPP and slow wave responses to empathic concern versus affective perspective taking. Left frontal activation (greater alpha suppression) while engaging in affective perspective taking was also related to higher levels of parent cognitive empathy. Together, this multilevel analysis demonstrates the important distinction between facets of empathy in children; the value of examining neurobehavioral processes in development. It provides provoking links between children's neural functioning and parental dispositions in early development. © 2017 John Wiley & Sons Ltd.

Synaptic Inputs Compete during Rapid Formation of the Calyx of Held: A New Model System for Neural Development

PubMed Central

Holcomb, Paul S.; Hoffpauir, Brian K.; Hoyson, Mitchell C.; Jackson, Dakota R.; Deerinck, Thomas J.; Marrs, Glenn S.; Dehoff, Marlin; Wu, Jonathan; Ellisman, Mark H.

2013-01-01

Hallmark features of neural circuit development include early exuberant innervation followed by competition and pruning to mature innervation topography. Several neural systems, including the neuromuscular junction and climbing fiber innervation of Purkinje cells, are models to study neural development in part because they establish a recognizable endpoint of monoinnervation of their targets and because the presynaptic terminals are large and easily monitored. We demonstrate here that calyx of Held (CH) innervation of its target, which forms a key element of auditory brainstem binaural circuitry, exhibits all of these characteristics. To investigate CH development, we made the first application of serial block-face scanning electron microscopy to neural development with fine temporal resolution and thereby accomplished the first time series for 3D ultrastructural analysis of neural circuit formation. This approach revealed a growth spurt of added apposed surface area (ASA) >200 μm2/d centered on a single age at postnatal day 3 in mice and an initial rapid phase of growth and competition that resolved to monoinnervation in two-thirds of cells within 3 d. This rapid growth occurred in parallel with an increase in action potential threshold, which may mediate selection of the strongest input as the winning competitor. ASAs of competing inputs were segregated on the cell body surface. These data suggest mechanisms to select “winning” inputs by regional reinforcement of postsynaptic membrane to mediate size and strength of competing synaptic inputs. PMID:23926251

Neural Network Classifies Teleoperation Data

NASA Technical Reports Server (NTRS)

Fiorini, Paolo; Giancaspro, Antonio; Losito, Sergio; Pasquariello, Guido

1994-01-01

Prototype artificial neural network, implemented in software, identifies phases of telemanipulator tasks in real time by analyzing feedback signals from force sensors on manipulator hand. Prototype is early, subsystem-level product of continuing effort to develop automated system that assists in training and supervising human control operator: provides symbolic feedback (e.g., warnings of impending collisions or evaluations of performance) to operator in real time during successive executions of same task. Also simplifies transition between teleoperation and autonomous modes of telerobotic system.

A behavioral framework to guide research on central auditory development and plasticity

PubMed Central

Sanes, Dan H.; Woolley, Sarah M. N.

2011-01-01

The auditory CNS is influenced profoundly by sounds heard during development. Auditory deprivation and augmented sound exposure can each perturb the maturation of neural computations as well as their underlying synaptic properties. However, we have learned little about the emergence of perceptual skills in these same model systems, and especially how perception is influenced by early acoustic experience. Here, we argue that developmental studies must take greater advantage of behavioral benchmarks. We discuss quantitative measures of perceptual development, and suggest how they can play a much larger role in guiding experimental design. Most importantly, including behavioral measures will allow us to establish empirical connections among environment, neural development, and perception. PMID:22196328

5-Mehtyltetrahydrofolate rescues alcohol-induced neural crest cell migration abnormalities.

PubMed

Shi, Yu; Li, Jiejing; Chen, Chunjiang; Gong, Manzi; Chen, Yuan; Liu, Youxue; Chen, Jie; Li, Tingyu; Song, Weihong

2014-09-16

Alcohol is detrimental to early development. Fetal alcohol spectrum disorders (FASD) due to maternal alcohol abuse results in a series of developmental abnormalities including cranial facial dysmorphology, ocular anomalies, congenital heart defects, microcephaly and intellectual disabilities. Previous studies have been shown that ethanol exposure causes neural crest (NC) apoptosis and perturbation of neural crest migration. However, the underlying mechanism remains elusive. In this report we investigated the fetal effect of alcohol on the process of neural crest development in the Xenopus leavis. Pre-gastrulation exposure of 2-4% alcohol induces apoptosis in Xenopus embryo whereas 1% alcohol specifically impairs neural crest migration without observing discernible apoptosis. Additionally, 1% alcohol treatment considerably increased the phenotype of small head (43.4% ± 4.4%, total embryo n = 234), and 1.5% and 2.0% dramatically augment the deformation to 81.2% ± 6.5% (n = 205) and 91.6% ± 3.0% (n = 235), respectively (P < 0.05). Significant accumulation of Homocysteine was caused by alcohol treatment in embryos and 5-mehtyltetrahydrofolate restores neural crest migration and alleviates homocysteine accumulation, resulting in inhibition of the alcohol-induced neurocristopathies. Our study demonstrates that prenatal alcohol exposure causes neural crest cell migration abnormality and 5-mehtyltetrahydrofolate could be beneficial for treating FASD.

Socioeconomic disadvantage and neural development from infancy through early childhood

PubMed Central

Chin-Lun Hung, Galen; Hahn, Jill; Alamiri, Bibi; Buka, Stephen L; Goldstein, Jill M; Laird, Nan; Nelson, Charles A; Smoller, Jordan W; Gilman, Stephen E

2015-01-01

Background: Early social experiences are believed to shape neurodevelopment, with potentially lifelong consequences. Yet minimal evidence exists regarding the role of the social environment on children’s neural functioning, a core domain of neurodevelopment. Methods: We analysed data from 36 443 participants in the United States Collaborative Perinatal Project, a socioeconomically diverse pregnancy cohort conducted between 1959 and 1974. Study outcomes included: physician (neurologist or paediatrician)-rated neurological abnormality neonatally and thereafter at 4 months and 1 and 7 years; indicators of neurological hard signs and soft signs; and indicators of autonomic nervous system function. Results: Children born to socioeconomically disadvantaged parents were more likely to exhibit neurological abnormalities at 4 months [odds ratio (OR) = 1.20; 95% confidence interval (CI) = 1.06, 1.37], 1 year (OR = 1.35; CI = 1.17, 1.56), and 7 years (OR = 1.67; CI = 1.48, 1.89), and more likely to exhibit neurological hard signs (OR = 1.39; CI = 1.10, 1.76), soft signs (OR = 1.26; CI = 1.09, 1.45) and autonomic nervous system dysfunctions at 7 years. Pregnancy and delivery complications, themselves associated with socioeconomic disadvantage, did not account for the higher risks of neurological abnormalities among disadvantaged children. Conclusions: Parental socioeconomic disadvantage was, independently from pregnancy and delivery complications, associated with abnormal child neural development during the first 7 years of life. These findings reinforce the importance of the early environment for neurodevelopment generally, and expand knowledge regarding the domains of neurodevelopment affected by environmental conditions. Further work is needed to determine the mechanisms linking socioeconomic disadvantage with children’s neural functioning, the timing of such mechanisms and their potential reversibility. PMID:26675752

Application of a neural network as a potential aid in predicting NTF pump failure

NASA Technical Reports Server (NTRS)

Rogers, James L.; Hill, Jeffrey S.; Lamarsh, William J., II; Bradley, David E.

1993-01-01

The National Transonic Facility has three centrifugal multi-stage pumps to supply liquid nitrogen to the wind tunnel. Pump reliability is critical to facility operation and test capability. A highly desirable goal is to be able to detect a pump rotating component problem as early as possible during normal operation and avoid serious damage to other pump components. If a problem is detected before serious damage occurs, the repair cost and downtime could be reduced significantly. A neural network-based tool was developed for monitoring pump performance and aiding in predicting pump failure. Once trained, neural networks can rapidly process many combinations of input values other than those used for training to approximate previously unknown output values. This neural network was applied to establish relationships among the critical frequencies and aid in predicting failures. Training pairs were developed from frequency scans from typical tunnel operations. After training, various combinations of critical pump frequencies were propagated through the neural network. The approximated output was used to create a contour plot depicting the relationships of the input frequencies to the output pump frequency.

The hypoxia factor Hif-1α controls neural crest chemotaxis and epithelial to mesenchymal transition

PubMed Central

Barriga, Elias H.; Maxwell, Patrick H.

2013-01-01

One of the most important mechanisms that promotes metastasis is the stabilization of Hif-1 (hypoxia-inducible transcription factor 1). We decided to test whether Hif-1α also was required for early embryonic development. We focused our attention on the development of the neural crest, a highly migratory embryonic cell population whose behavior has been likened to cancer metastasis. Inhibition of Hif-1α by antisense morpholinos in Xenopus laevis or zebrafish embryos led to complete inhibition of neural crest migration. We show that Hif-1α controls the expression of Twist, which in turn represses E-cadherin during epithelial to mesenchymal transition (EMT) of neural crest cells. Thus, Hif-1α allows cells to initiate migration by promoting the release of cell–cell adhesions. Additionally, Hif-1α controls chemotaxis toward the chemokine SDF-1 by regulating expression of its receptor Cxcr4. Our results point to Hif-1α as a novel and key regulator that integrates EMT and chemotaxis during migration of neural crest cells. PMID:23712262

Neural transcription factors bias cleavage stage blastomeres to give rise to neural ectoderm

PubMed Central

Gaur, Shailly; Mandelbaum, Max; Herold, Mona; Majumdar, Himani Datta; Neilson, Karen M.; Maynard, Thomas M.; Mood, Kathy; Daar, Ira O.; Moody, Sally A.

2016-01-01

The decision by embryonic ectoderm to give rise to epidermal versus neural derivatives is the result of signaling events during blastula and gastrula stages. However, there also is evidence in Xenopus that cleavage stage blastomeres contain maternally derived molecules that bias them toward a neural fate. We used a blastomere explant culture assay to test whether maternally deposited transcription factors bias 16-cell blastomere precursors of epidermal or neural ectoderm to express early zygotic neural genes in the absence of gastrulation interactions or exogenously supplied signaling factors. We found that Foxd4l1, Zic2, Gmnn and Sox11 each induced explants made from ventral, epidermis-producing blastomeres to express early neural genes, and that at least some of the Foxd4l1 and Zic2 activity is required at cleavage stages. Similarly, providing extra Foxd4l1 or Zic2 to explants made from dorsal, neural plate-producing blastomeres significantly increased expression of early neural genes, whereas knocking down either significantly reduced them. These results show that maternally delivered transcription factors bias cleavage stage blastomeres to a neural fate. We demonstrate that mouse and human homologues of Foxd4l1 have similar functional domains compared to the frog protein, as well as conserved transcriptional activities when expressed in Xenopus embryos and blastomere explants. PMID:27092474

Neonatal ghrelin programs development of hypothalamic feeding circuits

PubMed Central

Steculorum, Sophie M.; Collden, Gustav; Coupe, Berengere; Croizier, Sophie; Lockie, Sarah; Andrews, Zane B.; Jarosch, Florian; Klussmann, Sven; Bouret, Sebastien G.

2015-01-01

A complex neural network regulates body weight and energy balance, and dysfunction in the communication between the gut and this neural network is associated with metabolic diseases, such as obesity. The stomach-derived hormone ghrelin stimulates appetite through interactions with neurons in the arcuate nucleus of the hypothalamus (ARH). Here, we evaluated the physiological and neurobiological contribution of ghrelin during development by specifically blocking ghrelin action during early postnatal development in mice. Ghrelin blockade in neonatal mice resulted in enhanced ARH neural projections and long-term metabolic effects, including increased body weight, visceral fat, and blood glucose levels and decreased leptin sensitivity. In addition, chronic administration of ghrelin during postnatal life impaired the normal development of ARH projections and caused metabolic dysfunction. Consistent with these observations, direct exposure of postnatal ARH neuronal explants to ghrelin blunted axonal growth and blocked the neurotrophic effect of the adipocyte-derived hormone leptin. Moreover, chronic ghrelin exposure in neonatal mice also attenuated leptin-induced STAT3 signaling in ARH neurons. Collectively, these data reveal that ghrelin plays an inhibitory role in the development of hypothalamic neural circuits and suggest that proper expression of ghrelin during neonatal life is pivotal for lifelong metabolic regulation. PMID:25607843

Alpha Asymmetry in Infants at Risk for Autism Spectrum Disorders

ERIC Educational Resources Information Center

Gabard-Durnam, Laurel; Tierney, Adrienne L.; Vogel-Farley, Vanessa; Tager-Flusberg, Helen; Nelson, Charles A.

2015-01-01

An emerging focus of research on autism spectrum disorder (ASD) targets the identification of early-developing ASD endophenotypes using infant siblings of affected children. One potential neural endophenotype is resting frontal electroencephalogram (EEG) alpha asymmetry, a metric of hemispheric organization. Here, we examined the development of…

Postretrieval Extinction in Adolescence Prevents Return of Juvenile Fear

ERIC Educational Resources Information Center

Jones, Carolyn E.; Monfils, Marie-H.

2016-01-01

Traumatic experiences early in life can contribute to the development of mood and anxiety disorders that manifest during adolescence and young adulthood. In young rats exposed to acute fear or stress, alterations in neural development can lead to enduring behavioral abnormalities. Here, we used a modified extinction intervention…

Early Development of Subcortical Regions Involved in Non-Cued Attention Switching

ERIC Educational Resources Information Center

Casey, B. J.; Davidson, Matthew C.; Hara, Yuko; Thomas, Kathleen M.; Martinez, Antigona; Galvan, Adriana; Halperin, Jeffrey M.; Rodriguez-Aranda, Claudia E.; Tottenham, Nim

2004-01-01

This study examined the cognitive and neural development of attention switching using a simple forced-choice attention task and functional magnetic resonance imaging. Fourteen children and adults made discriminations among stimuli based on either shape or color. Performance on these trials was compared to performance during blocked trials…

A Brain for Speech. Evolutionary Continuity in Primate and Human Auditory-Vocal Processing

PubMed Central

Aboitiz, Francisco

2018-01-01

In this review article, I propose a continuous evolution from the auditory-vocal apparatus and its mechanisms of neural control in non-human primates, to the peripheral organs and the neural control of human speech. Although there is an overall conservatism both in peripheral systems and in central neural circuits, a few changes were critical for the expansion of vocal plasticity and the elaboration of proto-speech in early humans. Two of the most relevant changes were the acquisition of direct cortical control of the vocal fold musculature and the consolidation of an auditory-vocal articulatory circuit, encompassing auditory areas in the temporoparietal junction and prefrontal and motor areas in the frontal cortex. This articulatory loop, also referred to as the phonological loop, enhanced vocal working memory capacity, enabling early humans to learn increasingly complex utterances. The auditory-vocal circuit became progressively coupled to multimodal systems conveying information about objects and events, which gradually led to the acquisition of modern speech. Gestural communication accompanies the development of vocal communication since very early in human evolution, and although both systems co-evolved tightly in the beginning, at some point speech became the main channel of communication. PMID:29636657

Quantitative Analysis of Human Pluripotency and Neural Specification by In-Depth (Phospho)Proteomic Profiling.

PubMed

Singec, Ilyas; Crain, Andrew M; Hou, Junjie; Tobe, Brian T D; Talantova, Maria; Winquist, Alicia A; Doctor, Kutbuddin S; Choy, Jennifer; Huang, Xiayu; La Monaca, Esther; Horn, David M; Wolf, Dieter A; Lipton, Stuart A; Gutierrez, Gustavo J; Brill, Laurence M; Snyder, Evan Y

2016-09-13

Controlled differentiation of human embryonic stem cells (hESCs) can be utilized for precise analysis of cell type identities during early development. We established a highly efficient neural induction strategy and an improved analytical platform, and determined proteomic and phosphoproteomic profiles of hESCs and their specified multipotent neural stem cell derivatives (hNSCs). This quantitative dataset (nearly 13,000 proteins and 60,000 phosphorylation sites) provides unique molecular insights into pluripotency and neural lineage entry. Systems-level comparative analysis of proteins (e.g., transcription factors, epigenetic regulators, kinase families), phosphorylation sites, and numerous biological pathways allowed the identification of distinct signatures in pluripotent and multipotent cells. Furthermore, as predicted by the dataset, we functionally validated an autocrine/paracrine mechanism by demonstrating that the secreted protein midkine is a regulator of neural specification. This resource is freely available to the scientific community, including a searchable website, PluriProt. Published by Elsevier Inc.

An essential role for LPA signalling in telencephalon development.

PubMed

Geach, Timothy J; Faas, Laura; Devader, Christelle; Gonzalez-Cordero, Anai; Tabler, Jacqueline M; Brunsdon, Hannah; Isaacs, Harry V; Dale, Leslie

2014-02-01

Lysophosphatidic acid (LPA) has wide-ranging effects on many different cell types, acting through G-protein-coupled receptors such as LPAR6. We show that Xenopus lpar6 is expressed from late blastulae and is enriched in the mesoderm and dorsal ectoderm of early gastrulae. Expression in gastrulae is an early response to FGF signalling. Transcripts for lpar6 are enriched in the neural plate of Xenopus neurulae and loss of function caused forebrain defects, with reduced expression of telencephalic markers (foxg1, emx1 and nkx2-1). Midbrain (en2) and hindbrain (egr2) markers were unaffected. Foxg1 expression requires LPAR6 within ectoderm and not mesoderm. Head defects caused by LPAR6 loss of function were enhanced by co-inhibiting FGF signalling, with defects extending into the hindbrain (en2 and egr2 expression reduced). This is more severe than expected from simple summation of individual defects, suggesting that LPAR6 and FGF have overlapping or partially redundant functions in the anterior neural plate. We observed similar defects in forebrain development in loss-of-function experiments for ENPP2, an enzyme involved in the synthesis of extracellular LPA. Our study demonstrates a role for LPA in early forebrain development.

The intersection of stress, drug abuse and development.

PubMed

Thadani, Pushpa V

2002-01-01

Use or abuse of licit and illicit substances is often associated with environmental stress. Current clinical evidence clearly demonstrates neurobehavioral, somatic growth and developmental deficits in children born to drug-using mothers. However, the effects of environmental stress and its interaction with prenatal drug exposure on a child's development is unknown. Studies in pregnant animals under controlled conditions show drug-induced long-term alterations in brain structures and functions of the offspring. These cytoarchitecture alterations in the brain are often associated with perturbations in neurotransmitter systems that are intimately involved in the regulation of the stress responses. Similar abnormalities have been observed in the brains of animals exposed to other adverse exogenous (e.g., environmental stress) and/or endogenous (e.g., glucocorticoids) experiences during early life. The goal of this article is to: (1) provide evidence and a perspective that common neural systems are influenced during development both by perinatal drug exposure and early stress exposure; and (2) identify gaps and encourage new research examining the effects of early stress and perinatal drug exposure, in animal models, that would elucidate how stress- and drug-induced perturbations in neural systems influence later vulnerability to abused drugs in adult offspring.

[Molecular cloning, expression of rat Msx-1 and Msx-2 during early embryo genesis and roles for mandibular chondrogenesis].

PubMed

Ishiguro, S

1999-03-01

Quail-chick chimera experiments have shown a contribution of carnial neural crest cells to the craniofacial skeletal elements. Moreover, tissue interactions between epithelial-mesenchymal interaction during early facial process development are required for both skeletal differentiation and morphogenesis. In this study, it was observed that Msx homeobox containing genes expressed in the facial process were important molecules of cartilage morphogenesis. Rat cDNAs were isolated and encoded by Msx-1 and -2, and then the expression patterns using in situ hybridization were investigated during early rat face development. These genes were correlatively expressed in the cranial neural crest forming area (E 9.5 dpc) and the facial process (E 12.5 dpc). Antisence inhibition of Msx genes in the E 12.5 mandibular process exhibited the alteration of their gene expression and cartilage patterns. Antisence inhibition of Msx-1 induced lack of the medial portion of cartilage, and antisence inhibition of Msx-2 enhanced chondrogenesis of mandibular process under the organ culture condition. Thus it was concluded that expression of Msx genes during mandibular process development comprises important signals of chondrogenesis.

Selective and Efficient Neural Coding of Communication Signals Depends on Early Acoustic and Social Environment

PubMed Central

Amin, Noopur; Gastpar, Michael; Theunissen, Frédéric E.

2013-01-01

Previous research has shown that postnatal exposure to simple, synthetic sounds can affect the sound representation in the auditory cortex as reflected by changes in the tonotopic map or other relatively simple tuning properties, such as AM tuning. However, their functional implications for neural processing in the generation of ethologically-based perception remain unexplored. Here we examined the effects of noise-rearing and social isolation on the neural processing of communication sounds such as species-specific song, in the primary auditory cortex analog of adult zebra finches. Our electrophysiological recordings reveal that neural tuning to simple frequency-based synthetic sounds is initially established in all the laminae independent of patterned acoustic experience; however, we provide the first evidence that early exposure to patterned sound statistics, such as those found in native sounds, is required for the subsequent emergence of neural selectivity for complex vocalizations and for shaping neural spiking precision in superficial and deep cortical laminae, and for creating efficient neural representations of song and a less redundant ensemble code in all the laminae. Our study also provides the first causal evidence for ‘sparse coding’, such that when the statistics of the stimuli were changed during rearing, as in noise-rearing, that the sparse or optimal representation for species-specific vocalizations disappeared. Taken together, these results imply that a layer-specific differential development of the auditory cortex requires patterned acoustic input, and a specialized and robust sensory representation of complex communication sounds in the auditory cortex requires a rich acoustic and social environment. PMID:23630587

Maternal thyroid hormones are essential for neural development in zebrafish.

PubMed

Campinho, Marco A; Saraiva, João; Florindo, Claudia; Power, Deborah M

2014-07-01

Teleost eggs contain an abundant store of maternal thyroid hormones (THs), and early in zebrafish embryonic development, all the genes necessary for TH signaling are expressed. Nonetheless the function of THs in embryonic development remains elusive. To test the hypothesis that THs are fundamental for zebrafish embryonic development, an monocarboxilic transporter 8 (Mct8) knockdown strategy was deployed to prevent maternal TH uptake. Absence of maternal THs did not affect early specification of the neural epithelia but profoundly modified later dorsal specification of the brain and spinal cord as well as specific neuron differentiation. Maternal THs acted upstream of pax2a, pax7, and pax8 genes but downstream of shha and fgf8a signaling. The lack of inhibitory spinal cord interneurons and increased motoneurons in the mct8 morphants is consistent with their stiff axial body and impaired mobility. The mct8 mutations are associated with X-linked mental retardation in humans, and the cellular and molecular consequences of MCT8 knockdown during embryonic development in zebrafish provides new insight into the potential role of THs in this condition.

Maternal Thyroid Hormones Are Essential for Neural Development in Zebrafish

PubMed Central

Saraiva, João; Florindo, Claudia; Power, Deborah M.

2014-01-01

Teleost eggs contain an abundant store of maternal thyroid hormones (THs), and early in zebrafish embryonic development, all the genes necessary for TH signaling are expressed. Nonetheless the function of THs in embryonic development remains elusive. To test the hypothesis that THs are fundamental for zebrafish embryonic development, an monocarboxilic transporter 8 (Mct8) knockdown strategy was deployed to prevent maternal TH uptake. Absence of maternal THs did not affect early specification of the neural epithelia but profoundly modified later dorsal specification of the brain and spinal cord as well as specific neuron differentiation. Maternal THs acted upstream of pax2a, pax7, and pax8 genes but downstream of shha and fgf8a signaling. The lack of inhibitory spinal cord interneurons and increased motoneurons in the mct8 morphants is consistent with their stiff axial body and impaired mobility. The mct8 mutations are associated with X-linked mental retardation in humans, and the cellular and molecular consequences of MCT8 knockdown during embryonic development in zebrafish provides new insight into the potential role of THs in this condition. PMID:24877564

Vestigial-like 3 is a novel Ets1 interacting partner and regulates trigeminal nerve formation and cranial neural crest migration.

PubMed

Simon, Emilie; Thézé, Nadine; Fédou, Sandrine; Thiébaud, Pierre; Faucheux, Corinne

2017-10-15

Drosophila Vestigial is the founding member of a protein family containing a highly conserved domain, called Tondu, which mediates their interaction with members of the TEAD family of transcription factors (Scalloped in Drosophila ). In Drosophila , the Vestigial/Scalloped complex controls wing development by regulating the expression of target genes through binding to MCAT sequences. In vertebrates, there are four Vestigial-like genes, the functions of which are still not well understood. Here, we describe the regulation and function of vestigial-like 3 (vgll3) during Xenopus early development. A combination of signals, including FGF8, Wnt8a, Hoxa2, Hoxb2 and retinoic acid, limits vgll3 expression to hindbrain rhombomere 2. We show that vgll3 regulates trigeminal placode and nerve formation and is required for normal neural crest development by affecting their migration and adhesion properties. At the molecular level, vgll3 is a potent activator of pax3 , zic1 , Wnt and FGF , which are important for brain patterning and neural crest cell formation. Vgll3 interacts in the embryo with Tead proteins but unexpectedly with Ets1, with which it is able to stimulate a MCAT driven luciferase reporter gene. Our findings highlight a critical function for vgll3 in vertebrate early development. © 2017. Published by The Company of Biologists Ltd.

Generation of structures formed by lens and retinal cells differentiating from embryonic stem cells.

PubMed

Hirano, Mariko; Yamamoto, Akitsugu; Yoshimura, Naoko; Tokunaga, Tomoyuki; Motohashi, Tsutomu; Ishizaki, Katsuhiko; Yoshida, Hisahiro; Okazaki, Kenji; Yamazaki, Hidetoshi; Hayashi, Shin-Ichi; Kunisada, Takahiro

2003-12-01

Embryonic stem cells have the potential to give rise to all cell lineages when introduced into the early embryo. They also give rise to a limited number of different cell types in vitro in specialized culture systems. In this study, we established a culture system in which a structure consisting of lens, neural retina, and pigmented retina was efficiently induced from embryonic stem cells. Refractile cell masses containing lens and neural retina were surrounded by retinal pigment epithelium layers and, thus, designated as eye-like structures. Developmental processes required for eye development appear to proceed in this culture system, because the formation of the eye-like structures depended on the expression of Pax6, a key transcription factor for eye development. The present culture system opens up the possibility of examining early stages of eye development and also of producing cells for use in cellular therapy for various diseases of the eye. Copyright 2003 Wiley-Liss, Inc.

Epigenetic and Neural Circuitry Landscape of Psychotherapeutic Interventions

PubMed Central

2017-01-01

The science behind psychotherapy has garnered considerable interest, as objective measures are being developed to map the patient's subjective change over the course of treatment. Prenatal and early life influences have a lasting impact on how genes are expressed and the manner in which neural circuits are consolidated. Transgenerationally transmitted epigenetic markers as well as templates of enhanced thought flexibility versus evasion can be passed down from parent to child. This influences gene expression/repression (impacting neuroplasticity) and kindling of neurocircuitry which can perpetuate maladaptive cognitive processing seen in a number of psychiatric conditions. Importantly, genetic factors and the compounding effects of early life adversity do not inexorably lead to certain fated outcomes. The concepts of vulnerability and resilience are becoming more integrated into the framework of “differential susceptibility,” speaking to how corrective environmental factors may promote epigenetic change and reconfigure neural templates, allowing for symptomatic improvement. Psychotherapy is one such factor, and this review will focus on our current knowledge of its epigenetic and neurocircuitry impact. PMID:29226124

Cognitive Remediation for the Treatment of Cognitive Dysfunction in the Early Course of Psychosis.

PubMed

Lewandowski, Kathryn E

2016-01-01

The development of cognitive remediation programs has been a key step toward the creation of a treatment approach to address the cognitive-symptom domain in psychosis. Studies support the efficacy of cognitive remediation in producing moderate effects on cognition at the group level in patients with schizophrenia. Cognitive remediation may harness neuroplasticity in relevant systems that underpin the cognitive functions being addressed. Since neuroplasticity may be greater in people who (1) are younger and (2) have not yet experienced the consequences of long-term psychosis, cognitive remediation may be particularly effective in people in the early course of illness or in the prodrome, prior to the onset of frank symptoms. The present article reviews the evidence for implementing cognitive remediation in patients with recent-onset psychosis and people identified as being at high risk for developing schizophrenia, and also the evidence for cognitive remediation to modify neural targets. Promising findings suggest that cognitive remediation may be useful in addressing cognitive deficits in early-course and prodromal participants. Additionally, a growing literature using neuroimaging techniques demonstrates the ability of cognitive remediation paradigms to engage neural targets.

Older adults benefit from music training early in life: biological evidence for long-term training-driven plasticity.

PubMed

White-Schwoch, Travis; Woodruff Carr, Kali; Anderson, Samira; Strait, Dana L; Kraus, Nina

2013-11-06

Aging results in pervasive declines in nervous system function. In the auditory system, these declines include neural timing delays in response to fast-changing speech elements; this causes older adults to experience difficulty understanding speech, especially in challenging listening environments. These age-related declines are not inevitable, however: older adults with a lifetime of music training do not exhibit neural timing delays. Yet many people play an instrument for a few years without making a lifelong commitment. Here, we examined neural timing in a group of human older adults who had nominal amounts of music training early in life, but who had not played an instrument for decades. We found that a moderate amount (4-14 years) of music training early in life is associated with faster neural timing in response to speech later in life, long after training stopped (>40 years). We suggest that early music training sets the stage for subsequent interactions with sound. These experiences may interact over time to sustain sharpened neural processing in central auditory nuclei well into older age.

Older Adults Benefit from Music Training Early in Life: Biological Evidence for Long-Term Training-Driven Plasticity

PubMed Central

White-Schwoch, Travis; Carr, Kali Woodruff; Anderson, Samira; Strait, Dana L.

2013-01-01

Aging results in pervasive declines in nervous system function. In the auditory system, these declines include neural timing delays in response to fast-changing speech elements; this causes older adults to experience difficulty understanding speech, especially in challenging listening environments. These age-related declines are not inevitable, however: older adults with a lifetime of music training do not exhibit neural timing delays. Yet many people play an instrument for a few years without making a lifelong commitment. Here, we examined neural timing in a group of human older adults who had nominal amounts of music training early in life, but who had not played an instrument for decades. We found that a moderate amount (4–14 years) of music training early in life is associated with faster neural timing in response to speech later in life, long after training stopped (>40 years). We suggest that early music training sets the stage for subsequent interactions with sound. These experiences may interact over time to sustain sharpened neural processing in central auditory nuclei well into older age. PMID:24198359

Amphioxus and lamprey AP-2 genes: implications for neural crest evolution and migration patterns

NASA Technical Reports Server (NTRS)

Meulemans, Daniel; Bronner-Fraser, Marianne

2002-01-01

The neural crest is a uniquely vertebrate cell type present in the most basal vertebrates, but not in cephalochordates. We have studied differences in regulation of the neural crest marker AP-2 across two evolutionary transitions: invertebrate to vertebrate, and agnathan to gnathostome. Isolation and comparison of amphioxus, lamprey and axolotl AP-2 reveals its extensive expansion in the vertebrate dorsal neural tube and pharyngeal arches, implying co-option of AP-2 genes by neural crest cells early in vertebrate evolution. Expression in non-neural ectoderm is a conserved feature in amphioxus and vertebrates, suggesting an ancient role for AP-2 genes in this tissue. There is also common expression in subsets of ventrolateral neurons in the anterior neural tube, consistent with a primitive role in brain development. Comparison of AP-2 expression in axolotl and lamprey suggests an elaboration of cranial neural crest patterning in gnathostomes. However, migration of AP-2-expressing neural crest cells medial to the pharyngeal arch mesoderm appears to be a primitive feature retained in all vertebrates. Because AP-2 has essential roles in cranial neural crest differentiation and proliferation, the co-option of AP-2 by neural crest cells in the vertebrate lineage was a potentially crucial event in vertebrate evolution.

Neural Language Processing in Adolescent First-Language Learners

PubMed Central

Ferjan Ramirez, Naja; Leonard, Matthew K.; Torres, Christina; Hatrak, Marla; Halgren, Eric; Mayberry, Rachel I.

2014-01-01

The relation between the timing of language input and development of neural organization for language processing in adulthood has been difficult to tease apart because language is ubiquitous in the environment of nearly all infants. However, within the congenitally deaf population are individuals who do not experience language until after early childhood. Here, we investigated the neural underpinnings of American Sign Language (ASL) in 2 adolescents who had no sustained language input until they were approximately 14 years old. Using anatomically constrained magnetoencephalography, we found that recently learned signed words mainly activated right superior parietal, anterior occipital, and dorsolateral prefrontal areas in these 2 individuals. This spatiotemporal activity pattern was significantly different from the left fronto-temporal pattern observed in young deaf adults who acquired ASL from birth, and from that of hearing young adults learning ASL as a second language for a similar length of time as the cases. These results provide direct evidence that the timing of language experience over human development affects the organization of neural language processing. PMID:23696277

Ultrasmall implantable composite microelectrodes with bioactive surfaces for chronic neural interfaces

PubMed Central

Kozai, Takashi D. Yoshida; Langhals, Nicholas B.; Patel, Paras R.; Deng, Xiaopei; Zhang, Huanan; Smith, Karen L.; Lahann, Joerg; Kotov, Nicholas A.; Kipke, Daryl R.

2012-01-01

Implantable neural microelectrodes that can record extracellular biopotentials from small, targeted groups of neurons are critical for neuroscience research and emerging clinical applications including brain-controlled prosthetic devices. The crucial material-dependent problem is developing microelectrodes that record neural activity from the same neurons for years with high fidelity and reliability. Here, we report the development of an integrated composite electrode consisting of a carbon-fibre core, a poly(p-xylylene)-based thin-film coating that acts as a dielectric barrier and that is functionalized to control intrinsic biological processes, and a poly(thiophene)-based recording pad. The resulting implants are an order of magnitude smaller than traditional recording electrodes, and more mechanically compliant with brain tissue. They were found to elicit much reduced chronic reactive tissue responses and enabled single-neuron recording in acute and early chronic experiments in rats. This technology, taking advantage of new composites, makes possible highly selective and stealthy neural interface devices towards realizing long-lasting implants. PMID:23142839

Representational constraints on the development of memory and metamemory: a developmental-representational theory.

PubMed

Ceci, Stephen J; Fitneva, Stanka A; Williams, Wendy M

2010-04-01

Traditional accounts of memory development suggest that maturation of prefrontal cortex (PFC) enables efficient metamemory, which enhances memory. An alternative theory is described, in which changes in early memory and metamemory are mediated by representational changes, independent of PFC maturation. In a pilot study and Experiment 1, younger children failed to recognize previously presented pictures, yet the children could identify the context in which they occurred, suggesting these failures resulted from inefficient metamemory. Older children seldom exhibited such failure. Experiment 2 established that this was not due to retrieval-time recoding. Experiment 3 suggested that young children's representation of a picture's attributes explained their metamemory failure. Experiment 4 demonstrated that metamemory is age-invariant when representational quality is controlled: When stimuli were equivalently represented, age differences in memory and metamemory declined. These findings do not support the traditional view that as children develop, neural maturation permits more efficient monitoring, which leads to improved memory. These findings support a theory based on developmental-representational synthesis, in which constraints on metamemory are independent of neurological development; representational features drive early memory to a greater extent than previously acknowledged, suggesting that neural maturation has been overimputed as a source of early metamemory and memory failure. PsycINFO Database Record (c) 2010 APA, all rights reserved.

Neural Reward Processing Mediates the Relationship between Insomnia Symptoms and Depression in Adolescence.

PubMed

Casement, Melynda D; Keenan, Kate E; Hipwell, Alison E; Guyer, Amanda E; Forbes, Erika E

2016-02-01

Emerging evidence suggests that insomnia may disrupt reward-related brain function-a potentially important factor in the development of depressive disorder. Adolescence may be a period during which such disruption is especially problematic given the rise in the incidence of insomnia and ongoing development of neural systems that support reward processing. The present study uses longitudinal data to test the hypothesis that disruption of neural reward processing is a mechanism by which insomnia symptoms-including nocturnal insomnia symptoms (NIS) and nonrestorative sleep (NRS)-contribute to depressive symptoms in adolescent girls. Participants were 123 adolescent girls and their caregivers from an ongoing longitudinal study of precursors to depression across adolescent development. NIS and NRS were assessed annually from ages 9 to 13 years. Girls completed a monetary reward task during a functional MRI scan at age 16 years. Depressive symptoms were assessed at ages 16 and 17 years. Multivariable regression tested the prospective associations between NIS and NRS, neural response during reward anticipation, and the mean number of depressive symptoms (omitting sleep problems). NRS, but not NIS, during early adolescence was positively associated with late adolescent dorsal medial prefrontal cortex (dmPFC) response to reward anticipation and depressive symptoms. DMPFC response mediated the relationship between early adolescent NRS and late adolescent depressive symptoms. These results suggest that NRS may contribute to depression by disrupting reward processing via altered activity in a region of prefrontal cortex involved in affective control. The results also support the mechanistic differentiation of NIS and NRS. © 2016 Associated Professional Sleep Societies, LLC.

Future Directions in the Study of Early-Life Stress and Physical and Emotional Health: Implications of the Neuroimmune Network Hypothesis.

PubMed

Hostinar, Camelia E; Nusslock, Robin; Miller, Gregory E

2018-01-01

Early-life stress is associated with increased vulnerability to physical and emotional health problems across the lifespan. The recently developed neuroimmune network hypothesis proposes that one of the underlying mechanisms for these associations is that early-life stress amplifies bidirectional crosstalk between the brain and the immune system, contributing to several mental and physical health conditions that have inflammatory underpinnings, such as depression and coronary heart disease. Neuroimmune crosstalk is thought to perpetuate inflammation and neural alterations linked to early-life stress exposure, and also foster behaviors that can further compromise health, such as smoking, drug abuse and consumption of high-fat diets. The goal of the present review is to briefly summarize the neuroimmune network hypothesis and use it as a starting point for generating new questions about the role of early-life stress in establishing a dysregulated relationship between neural and immune signaling, with consequences for lifespan physical and emotional health. Specifically, we aim to discuss implications and future directions for theory and empirical research on early-life stress, as well as for interventions that may improve the health and well-being of children and adolescents living in adverse conditions.

GABA and Gap Junctions in the Development of Synchronized Activity in Human Pluripotent Stem Cell-Derived Neural Networks

PubMed Central

Mäkinen, Meeri Eeva-Liisa; Ylä-Outinen, Laura; Narkilahti, Susanna

2018-01-01

The electrical activity of the brain arises from single neurons communicating with each other. However, how single neurons interact during early development to give rise to neural network activity remains poorly understood. We studied the emergence of synchronous neural activity in human pluripotent stem cell (hPSC)-derived neural networks simultaneously on a single-neuron level and network level. The contribution of gamma-aminobutyric acid (GABA) and gap junctions to the development of synchronous activity in hPSC-derived neural networks was studied with GABA agonist and antagonist and by blocking gap junctional communication, respectively. We characterized the dynamics of the network-wide synchrony in hPSC-derived neural networks with high spatial resolution (calcium imaging) and temporal resolution microelectrode array (MEA). We found that the emergence of synchrony correlates with a decrease in very strong GABA excitation. However, the synchronous network was found to consist of a heterogeneous mixture of synchronously active cells with variable responses to GABA, GABA agonists and gap junction blockers. Furthermore, we show how single-cell distributions give rise to the network effect of GABA, GABA agonists and gap junction blockers. Finally, based on our observations, we suggest that the earliest form of synchronous neuronal activity depends on gap junctions and a decrease in GABA induced depolarization but not on GABAA mediated signaling. PMID:29559893

Flank wears Simulation by using back propagation neural network when cutting hardened H-13 steel in CNC End Milling

NASA Astrophysics Data System (ADS)

Hazza, Muataz Hazza F. Al; Adesta, Erry Y. T.; Riza, Muhammad

2013-12-01

High speed milling has many advantages such as higher removal rate and high productivity. However, higher cutting speed increase the flank wear rate and thus reducing the cutting tool life. Therefore estimating and predicting the flank wear length in early stages reduces the risk of unaccepted tooling cost. This research presents a neural network model for predicting and simulating the flank wear in the CNC end milling process. A set of sparse experimental data for finish end milling on AISI H13 at hardness of 48 HRC have been conducted to measure the flank wear length. Then the measured data have been used to train the developed neural network model. Artificial neural network (ANN) was applied to predict the flank wear length. The neural network contains twenty hidden layer with feed forward back propagation hierarchical. The neural network has been designed with MATLAB Neural Network Toolbox. The results show a high correlation between the predicted and the observed flank wear which indicates the validity of the models.

Early Generalized Overgrowth in Autism Spectrum Disorder: Prevalence Rates, Gender Effects, and Clinical Outcomes

PubMed Central

Campbell, Daniel J.; Chang, Joseph; Chawarska, Katarzyna

2014-01-01

Objective Although early head and body overgrowth have been well-documented in autism spectrum disorder (ASD), their prevalence and significance remain unclear. It is also unclear whether overgrowth affects males and females differentially, and whether it is associated with clinical outcomes later in life. Method To evaluate prevalence of somatic overgrowth, gender effects, and associations with clinical outcomes, head circumference, height, and weight measurements were collected retrospectively between birth and 2 years of age in toddlers with ASD (n=200) and typically developing (TD; n=147) community controls. Symptom severity, verbal, and nonverbal functioning were assessed at 4 years. Results Abnormalities in somatic growth in infants with ASD were consistent with early generalized overgrowth (EGO). Boys but not girls with ASD were larger and exhibited an increased rate of extreme EGO compared to community controls (18.0% versus 3.4%). Presence of a larger body at birth and postnatal overgrowth were associated independently with poorer social, verbal, and nonverbal skills at 4 years. Conclusion Although early growth abnormalities in ASD are less common than previously thought, their presence is predictive of lower social, verbal, and nonverbal skills at 4 years, suggesting that they may constitute a biomarker for identifying toddlers with ASD at risk for less-optimal outcomes. The results highlight that the search for mechanisms underlying atypical brain development in ASD should consider factors responsible for both neural and non-neural tissue development during prenatal and early postnatal periods, and can be informed by the finding that early overgrowth may be more readily observed in males than females with ASD. PMID:25245350

A microinjection technique for targeting regions of embryonic and neonatal mouse brain in vivo

PubMed Central

Davidson, Steve; Truong, Hai; Nakagawa, Yasushi; Giesler, Glenn J

2009-01-01

A simple pressure injection technique was developed to deliver substances into specific regions of the embryonic and neonatal mouse brain in vivo. The retrograde tracers Fluorogold and cholera toxin B subunit were used to test the validity of the technique. Injected animals survived the duration of transport (24–48 hrs) and then were sacrificed and perfused with fixative. Small injections (≤ 50 nL) were contained within targeted structures of the perinatal brain and labeled distant cells of origin in several model neural pathways. Traced neural pathways in the perinatal mouse were further examined with immunohistochemical methods to test the feasibility of double labeling experiments during development. Several experimental situations in which this technique would be useful are discussed, for example, to label projection neurons in slice or culture preparations of mouse embryos and neonates. The administration of pharmacological or genetic vectors directly into specific neural targets during development should also be feasible. An examination of the form of neural pathways during early stages of life may lead to insights regarding the functional changes that occur during critical periods of development and provide an anatomic basis for some neurodevelopmental disorders. PMID:19840780

Early distinction system of mine fire in underground by using a neural-network system

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ohga, Kotaro; Higuchi, Kiyoshi

1996-12-31

In our laboratory, a new detection system using smell detectors was developed to detect the spontaneous combustion of coal and the combustion of other materials used underground. The results of experiments clearly the combustion of materials can be detected earlier by this detection system than by conventional detectors for gas and smoke, and there were significant differences between output data from each smell detector for coal, rubber, oil and wood. In order to discern the source of combustion gases, we have been developing a distinction system using a neural-network system. It has shown successful results in laboratory tests. This papermore » describes our detection system using smell detectors and our distinction system which uses a neural-network system, and presents results of experiments using both systems.« less

Investigating the extent of neuroplasticity: Writing in children with perinatal stroke.

PubMed

Woolpert, Darin; Reilly, Judy S

2016-08-01

The developing brain is remarkably plastic, as evidenced by language studies of children with perinatal stroke (PS). Despite initial delays and in contrast to adults with comparable lesions, children with PS perform comparably to their age-matched peers in free conversation by school age. Recent studies of spoken language in older children with PS have indicated limits to neural plasticity. Writing, a cognitively demanding and language dependent domain, is understudied in children with PS. Investigating writing development will provide another perspective on the continuing linguistic development in this population. Written language performance in 43 children with PS and 60 of their typically-developing (TD) peers was evaluated to further investigate the breadth and limits to neural plasticity. Two tasks of varying difficulty were administered: a picture description, which provided a referent to facilitate writing for the children, and a more challenging autobiographical narrative. Texts were analyzed across three broad writing dimensions - productivity, complexity, and linguistic accuracy. Group differences were primarily found on accuracy indices. Morphological accuracy was most impacted by early brain injury and older children with PS did not have higher morphological accuracy than their younger counterparts, suggesting limited development with age. There were no differences in performance based on hemisphere of lesion. In addition to enhancing our understanding of long-term language outcomes in children with PS, the results further illuminate the extent and limitations of early neural plasticity for language. Copyright © 2016 Elsevier Ltd. All rights reserved.

Neural crest-specific deletion of Ldb1 leads to cleft secondary palate with impaired palatal shelf elevation

PubMed Central

2014-01-01

Background LIM domain binding protein 1 (LDB1) is a transcriptional co-factor, which interacts with multiple transcription factors and other proteins containing LIM domains. Complete inactivation of Ldb1 in mice resulted in early embryonic lethality with severe patterning defects during gastrulation. Tissue-specific deletions using a conditional knockout allele revealed additional roles of Ldb1 in the development of the central nervous system, hematopoietic system, and limbs. The goal of the current study was to determine the importance of Ldb1 function during craniofacial development in mouse embryos. Results We generated tissue-specific Ldb1 mutants using Wnt1-Cre, which causes deletion of a floxed allele in the neural crest; neural crest-derived cells contribute to most of the mesenchyme of the developing face. All examined Wnt1-Cre;Ldb1 fl/- mutants suffered from cleft secondary palate. Therefore, we performed a series of experiments to investigate how Ldb1 regulated palate development. First, we examined the expression of Ldb1 during normal development, and found that Ldb1 was expressed broadly in the palatal mesenchyme during early stages of palate development. Second, we compared the morphology of the developing palate in control and Ldb1 mutant embryos using sections. We found that the mutant palatal shelves had abnormally blunt appearance, and failed to elevate above the tongue at the posterior domain. An in vitro head culture experiment indicated that the elevation defect was not due to interference by the tongue. Finally, in the Ldb1 mutant palatal shelves, cell proliferation was abnormal in the anterior, and the expression of Wnt5a, Pax9 and Osr2, which regulate palatal shelf elevation, was also altered. Conclusions The function of Ldb1 in the neural crest-derived palatal mesenchyme is essential for normal morphogenesis of the secondary palate. PMID:24433583

Myogenic specification in somites: induction by axial structures.

PubMed

Buffinger, N; Stockdale, F E

1994-06-01

Specification of the myogenic phenotype in somites was examined in the early chick embryo using organotypic explant cultures stained with monoclonal antibodies to myosin heavy chain. It was found that myogenic specification (formation of muscle fibers in explants of somites or segmental plates cultured alone) does not occur until Hamburger and Hamilton stage 11 (12-14 somites). At this stage, only the somites in the rostral half of the embryo are myogenically specified. By Hamburger and Hamilton stage 12 (15-17 somites), the three most caudal somites were not specified to be myogenic while most or all of the more rostral somites are specified to myogenesis. Somites from older embryos (stage 13-15, 18-26 somites) showed the same pattern of myogenic specification--all but the three most caudal somites were specified. We investigated the effects of the axial structures, the notochord and neural tube, on myogenic specification. Both the notochord and neural tube were able to induce myogenesis in unspecified somites. In contrast, the neural tube, but not the notochord, was able to induce myogenesis in explants of segmental plate, a structure which is not myogenic when cultured alone. When explants of specified somites were stained with antibodies to slow or fast MyHC, it was found that myofiber diversity (fast and fast slow fibers) was established very early in development (as early as Hamburger and Hamilton stage 11). We also found fiber diversity in explants of unspecified somites (the three most caudal somites from stage 11 to 15) when they were recombined with notochord or neural tube. We conclude that myogenic specification in the embryo results in diverse fiber types and is an inductive process which is mediated by factors produced by the neural tube and notochord.

Learning representations for the early detection of sepsis with deep neural networks.

PubMed

Kam, Hye Jin; Kim, Ha Young

2017-10-01

Sepsis is one of the leading causes of death in intensive care unit patients. Early detection of sepsis is vital because mortality increases as the sepsis stage worsens. This study aimed to develop detection models for the early stage of sepsis using deep learning methodologies, and to compare the feasibility and performance of the new deep learning methodology with those of the regression method with conventional temporal feature extraction. Study group selection adhered to the InSight model. The results of the deep learning-based models and the InSight model were compared. With deep feedforward networks, the area under the ROC curve (AUC) of the models were 0.887 and 0.915 for the InSight and the new feature sets, respectively. For the model with the combined feature set, the AUC was the same as that of the basic feature set (0.915). For the long short-term memory model, only the basic feature set was applied and the AUC improved to 0.929 compared with the existing 0.887 of the InSight model. The contributions of this paper can be summarized in three ways: (i) improved performance without feature extraction using domain knowledge, (ii) verification of feature extraction capability of deep neural networks through comparison with reference features, and (iii) improved performance with feedforward neural networks using long short-term memory, a neural network architecture that can learn sequential patterns. Copyright © 2017 Elsevier Ltd. All rights reserved.

IDENTIFICATION OF NEURAL BIOMARKERS OF ALTERED SEXUAL DIFFERENTIATION FOLLOWING GESTATIONAL EXPOSURE***

EPA Science Inventory

Sexual differentiation of the brain occurs during late gestation through the early postnatal period. The development of the phenotypical male brain is dependent on the aromatization of circulating testosterone to estradiol. Exposure to endocrine disrupting chemicals (EDCs) duri...

Identification of neural biomarkers of altered sexual differentiation following gestational exposure

EPA Science Inventory

Sexual differentiation of the brain occurs during late gestation through the early postnatal period. The development of the phenotypical male brain is dependent on the aromatization of circulating testosterone to estradiol. Exposure to endocrine disrupting chemicals (EDCs) during...

Identification of neural biomarkers of altered sexual differentiation following gestational exposure###

EPA Science Inventory

Sexual differentiation of the brain occurs during late gestation through the early postnatal period. The development of the phenotypical male brain is dependent on the aromatization of circulating testosterone to estradiol. Exposure to endocrine disrupting chemicals (EDCs) duri...

Experience-dependent emergence of beta and gamma band oscillations in the primary visual cortex during the critical period

PubMed Central

Chen, Guang; Rasch, Malte J.; Wang, Ran; Zhang, Xiao-hui

2015-01-01

Neural oscillatory activities have been shown to play important roles in neural information processing and the shaping of circuit connections during development. However, it remains unknown whether and how specific neural oscillations emerge during a postnatal critical period (CP), in which neuronal connections are most substantially modified by neural activity and experience. By recording local field potentials (LFPs) and single unit activity in developing primary visual cortex (V1) of head-fixed awake mice, we here demonstrate an emergence of characteristic oscillatory activities during the CP. From the pre-CP to CP, the peak frequency of spontaneous fast oscillatory activities shifts from the beta band (15–35 Hz) to the gamma band (40–70 Hz), accompanied by a decrease of cross-frequency coupling (CFC) and broadband spike-field coherence (SFC). Moreover, visual stimulation induced a large increase of beta-band activity but a reduction of gamma-band activity specifically from the CP onwards. Dark rearing of animals from the birth delayed this emergence of oscillatory activities during the CP, suggesting its dependence on early visual experience. These findings suggest that the characteristic neuronal oscillatory activities emerged specifically during the CP may represent as neural activity trait markers for the experience-dependent maturation of developing visual cortical circuits. PMID:26648548

An Implantable Wireless Neural Interface for Recording Cortical Circuit Dynamics in Moving Primates

PubMed Central

Borton, David A.; Yin, Ming; Aceros, Juan; Nurmikko, Arto

2013-01-01

Objective Neural interface technology suitable for clinical translation has the potential to significantly impact the lives of amputees, spinal cord injury victims, and those living with severe neuromotor disease. Such systems must be chronically safe, durable, and effective. Approach We have designed and implemented a neural interface microsystem, housed in a compact, subcutaneous, and hermetically sealed titanium enclosure. The implanted device interfaces the brain with a 510k-approved, 100-element silicon-based MEA via a custom hermetic feedthrough design. Full spectrum neural signals were amplified (0.1Hz to 7.8kHz, ×200 gain) and multiplexed by a custom application specific integrated circuit, digitized, and then packaged for transmission. The neural data (24 Mbps) was transmitted by a wireless data link carried on an frequency shift key modulated signal at 3.2GHz and 3.8GHz to a receiver 1 meter away by design as a point-to-point communication link for human clinical use. The system was powered by an embedded medical grade rechargeable Li-ion battery for 7-hour continuous operation between recharge via an inductive transcutaneous wireless power link at 2MHz. Main results Device verification and early validation was performed in both swine and non-human primate freely-moving animal models and showed that the wireless implant was electrically stable, effective in capturing and delivering broadband neural data, and safe for over one year of testing. In addition, we have used the multichannel data from these mobile animal models to demonstrate the ability to decode neural population dynamics associated with motor activity. Significance We have developed an implanted wireless broadband neural recording device evaluated in non-human primate and swine. The use of this new implantable neural interface technology can provide insight on how to advance human neuroprostheses beyond the present early clinical trials. Further, such tools enable mobile patient use, have the potential for wider diagnosis of neurological conditions, and will advance brain research. PMID:23428937

An implantable wireless neural interface for recording cortical circuit dynamics in moving primates

NASA Astrophysics Data System (ADS)

Borton, David A.; Yin, Ming; Aceros, Juan; Nurmikko, Arto

2013-04-01

Objective. Neural interface technology suitable for clinical translation has the potential to significantly impact the lives of amputees, spinal cord injury victims and those living with severe neuromotor disease. Such systems must be chronically safe, durable and effective. Approach. We have designed and implemented a neural interface microsystem, housed in a compact, subcutaneous and hermetically sealed titanium enclosure. The implanted device interfaces the brain with a 510k-approved, 100-element silicon-based microelectrode array via a custom hermetic feedthrough design. Full spectrum neural signals were amplified (0.1 Hz to 7.8 kHz, 200× gain) and multiplexed by a custom application specific integrated circuit, digitized and then packaged for transmission. The neural data (24 Mbps) were transmitted by a wireless data link carried on a frequency-shift-key-modulated signal at 3.2 and 3.8 GHz to a receiver 1 m away by design as a point-to-point communication link for human clinical use. The system was powered by an embedded medical grade rechargeable Li-ion battery for 7 h continuous operation between recharge via an inductive transcutaneous wireless power link at 2 MHz. Main results. Device verification and early validation were performed in both swine and non-human primate freely-moving animal models and showed that the wireless implant was electrically stable, effective in capturing and delivering broadband neural data, and safe for over one year of testing. In addition, we have used the multichannel data from these mobile animal models to demonstrate the ability to decode neural population dynamics associated with motor activity. Significance. We have developed an implanted wireless broadband neural recording device evaluated in non-human primate and swine. The use of this new implantable neural interface technology can provide insight into how to advance human neuroprostheses beyond the present early clinical trials. Further, such tools enable mobile patient use, have the potential for wider diagnosis of neurological conditions and will advance brain research.

The Utility of EEG Band Power Analysis in the Study of Infancy and Early Childhood

PubMed Central

Saby, Joni N.; Marshall, Peter J.

2012-01-01

Research employing electroencephalographic (EEG) techniques with infants and young children has flourished in recent years due to increased interest in understanding the neural processes involved in early social and cognitive development. This review focuses on the functional characteristics of the alpha, theta, and gamma frequency bands in the developing EEG. Examples of how analyses of EEG band power have been applied to specific lines of developmental research are also discussed. These examples include recent work on the infant mu rhythm and action processing, frontal alpha asymmetry and approach-withdrawal tendencies, and EEG power measures in the study of early psychosocial adversity. PMID:22545661

Early event related fields during visually evoked pain anticipation.

PubMed

Gopalakrishnan, Raghavan; Burgess, Richard C; Plow, Ela B; Floden, Darlene P; Machado, Andre G

2016-03-01

Pain experience is not only a function of somatosensory inputs. Rather, it is strongly influenced by cognitive and affective pathways. Pain anticipatory phenomena, an important limitation to rehabilitative efforts in the chronic state, are processed by associative and limbic networks, along with primary sensory cortices. Characterization of neurophysiological correlates of pain anticipation, particularly during very early stages of neural processing is critical for development of therapeutic interventions. Here, we utilized magnetoencephalography to study early event-related fields (ERFs) in healthy subjects exposed to a 3 s visual countdown task that preceded a painful stimulus, a non-painful stimulus or no stimulus. We found that the first countdown cue, but not the last cue, evoked critical ERFs signaling anticipation, attention and alertness to the noxious stimuli. Further, we found that P2 and N2 components were significantly different in response to first-cues that signaled incoming painful stimuli when compared to non-painful or no stimuli. The findings indicate that early ERFs are relevant neural substrates of pain anticipatory phenomena and could be potentially serve as biomarkers. These measures could assist in the development of neurostimulation approaches aimed at curbing the negative effects of pain anticipation during rehabilitation. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

A Homolog of Subtilisin-Like Proprotein Convertase 7 Is Essential to Anterior Neural Development in Xenopus

PubMed Central

Senturker, Sema; Thomas, John Terrig; Mateshaytis, Jennifer; Moos, Malcolm

2012-01-01

Background Subtilisin-like Proprotein Convertase 7 (SPC7) is a member of the subtilisin/kexin family of pro-protein convertases. It cleaves many pro-proteins to release their active proteins, including members of the bone morphogenetic protein (BMP) family of signaling molecules. Other SPCs are known to be required during embryonic development but corresponding data regarding SPC7 have not been reported previously. Methodology/Principal Findings We demonstrated that Xenopus SPC7 (SPC7) was expressed predominantly in the developing brain and eye, throughout the neural plate initially, then more specifically in the lens and retina primordia as development progressed. Since no prior functional information has been reported for SPC7, we used gain- and loss-of-function experiments to investigate the possibility that it may also convey patterning or tissue specification information similarly to Furin, SPC4, and SPC6. Overexpression of SPC7 was without effect. In contrast, injection of SPC7 antisense morpholino oligonucleotides (MO) into a single blastomere at the 2- or 4-cell stage produced marked disruption of head structures; anophthalmia was salient. Bilateral injections suppressed head and eye formation completely. In parallel with suppression of eye and brain development by SPC7 knockdown, expression of early anterior neural markers (Sox2, Otx2, Rx2, and Pax6) and late eye-specific markers (β-Crystallin and Opsin), and of BMP target genes such as Tbx2 and Tbx3, was reduced or eliminated. Taken together, these findings suggest a critical role for SPC7–perhaps, at least in part, due to activation of one or more BMPs–in early patterning of the anterior neural plate and its derivatives. Conclusion/Significance SPC7 is required for normal development of the eye and brain, possibly through processing BMPs, though other potential substrates cannot be excluded. PMID:22761776

Neural Differentiation of Embryonic Stem Cells In Vitro: A Road Map to Neurogenesis in the Embryo

PubMed Central

Abranches, Elsa; Silva, Margarida; Pradier, Laurent; Schulz, Herbert; Hummel, Oliver; Henrique, Domingos; Bekman, Evguenia

2009-01-01

Background The in vitro generation of neurons from embryonic stem (ES) cells is a promising approach to produce cells suitable for neural tissue repair and cell-based replacement therapies of the nervous system. Available methods to promote ES cell differentiation towards neural lineages attempt to replicate, in different ways, the multistep process of embryonic neural development. However, to achieve this aim in an efficient and reproducible way, a better knowledge of the cellular and molecular events that are involved in the process, from the initial specification of neuroepithelial progenitors to their terminal differentiation into neurons and glial cells, is required. Methodology/Principal Findings In this work, we characterize the main stages and transitions that occur when ES cells are driven into a neural fate, using an adherent monolayer culture system. We established improved conditions to routinely produce highly homogeneous cultures of neuroepithelial progenitors, which organize into neural tube-like rosettes when they acquire competence for neuronal production. Within rosettes, neuroepithelial progenitors display morphological and functional characteristics of their embryonic counterparts, namely, apico-basal polarity, active Notch signalling, and proper timing of production of neurons and glia. In order to characterize the global gene activity correlated with each particular stage of neural development, the full transcriptome of different cell populations that arise during the in vitro differentiation protocol was determined by microarray analysis. By using embryo-oriented criteria to cluster the differentially expressed genes, we define five gene expression signatures that correlate with successive stages in the path from ES cells to neurons. These include a gene signature for a primitive ectoderm-like stage that appears after ES cells enter differentiation, and three gene signatures for subsequent stages of neural progenitor development, from an early stage that follows neural induction to a final stage preceding terminal differentiation. Conclusions/Significance Overall, our work confirms and extends the cellular and molecular parallels between monolayer ES cell neural differentiation and embryonic neural development, revealing in addition novel aspects of the genetic network underlying the multistep process that leads from uncommitted cells to differentiated neurons. PMID:19621087

Psychological and neural contributions to appetite self-regulation.

PubMed

Stoeckel, Luke E; Birch, Leann L; Heatherton, Todd; Mann, Traci; Hunter, Christine; Czajkowski, Susan; Onken, Lisa; Berger, Paige K; Savage, Cary R

2017-03-01

This paper reviews the state of the science on psychological and neural contributions to appetite self-regulation in the context of obesity. Three content areas (neural systems and cognitive functions; parenting and early childhood development; and goal setting and goal striving) served to illustrate different perspectives on the psychological and neural factors that contribute to appetite dysregulation in the context of obesity. Talks were initially delivered at an NIH workshop consisting of experts in these three content areas, and then content areas were further developed through a review of the literature. Self-regulation of appetite involves a complex interaction between multiple domains, including cognitive, neural, social, and goal-directed behaviors and decision-making. Self-regulation failures can arise from any of these factors, and the resulting implications for obesity should be considered in light of each domain. In some cases, self-regulation is amenable to intervention; however, this does not appear to be universally true, which has implications for both prevention and intervention efforts. Appetite regulation is a complex, multifactorial construct. When considering its role in the obesity epidemic, it is advisable to consider its various dimensions together to best inform prevention and treatment efforts. © 2017 The Obesity Society.

Psychological and Neural Contributions to Appetite Self-Regulation

PubMed Central

Stoeckel, Luke E.; Birch, Leann L.; Heatherton, Todd; Mann, Traci; Hunter, Christine; Czajkowski, Susan; Onken, Lisa; Berger, Paige K.; Savage, Cary R.

2017-01-01

Objective Review the state-of-the-science on psychological and neural contributions to appetite self-regulation in the context of obesity. Methods Three content areas (neural systems and cognitive functions; parenting and early childhood development; and goal setting and goal striving) served as examples of different perspectives on the psychological and neural factors that contribute to appetite dysregulation in the context of obesity. Talks were initially delivered at a workshop consisting of experts in these three content areas and then content areas were further developed through a review of the literature. Results Self-regulation of appetite involves a complex interaction between multiple domains, including cognitive, neural, social, and goal-directed behaviors and decision-making. Self-regulation failures can results from any of these factors, and the resulting implications for obesity should be considered in light of each domain. In some cases, self-regulation appears to be amenable to intervention; however, this does not appear to be universally true, which has implications for both prevention and intervention efforts. Conclusions Appetite regulation is a complex, multi-factorial construct. When considering its role in the obesity epidemic, it is advisable to consider these various contributions together to best inform prevention and treatment efforts. PMID:28229541

Predicate calculus for an architecture of multiple neural networks

NASA Astrophysics Data System (ADS)

Consoli, Robert H.

1990-08-01

Future projects with neural networks will require multiple individual network components. Current efforts along these lines are ad hoc. This paper relates the neural network to a classical device and derives a multi-part architecture from that model. Further it provides a Predicate Calculus variant for describing the location and nature of the trainings and suggests Resolution Refutation as a method for determining the performance of the system as well as the location of needed trainings for specific proofs. 2. THE NEURAL NETWORK AND A CLASSICAL DEVICE Recently investigators have been making reports about architectures of multiple neural networksL234. These efforts are appearing at an early stage in neural network investigations they are characterized by architectures suggested directly by the problem space. Touretzky and Hinton suggest an architecture for processing logical statements1 the design of this architecture arises from the syntax of a restricted class of logical expressions and exhibits syntactic limitations. In similar fashion a multiple neural netword arises out of a control problem2 from the sequence learning problem3 and from the domain of machine learning. 4 But a general theory of multiple neural devices is missing. More general attempts to relate single or multiple neural networks to classical computing devices are not common although an attempt is made to relate single neural devices to a Turing machines and Sun et a!. develop a multiple neural architecture that performs pattern classification.

HIGH-CONTENT ANALYSIS OF PRIMARY RAT NEURAL CORTICALCULTURES FOR DEVELOPMENTAL NEUROTOXICITY SCREENING

EPA Science Inventory

Development of the vertebrate nervous system proceeds through a number of critical processes, ultimately concluding with the extension of neurites and establishment of synaptic networks. Early-life exposure to toxicants that perturb these critical developmental processes can po...

A Translational Neuroscience Approach to Understanding the Development of Social Anxiety Disorder and its Pathophysiology

PubMed Central

Fox, Andrew S.; Kalin, Ned H.

2014-01-01

This review brings together recent research from molecular, neural circuit, animal model, and human studies to understand the neurodevelopmental mechanisms underlying Social Anxiety Disorder (SAD). SAD is common, debilitating, and often leads to further psychopathology. Numerous studies demonstrate that extremely behaviorally inhibited and temperamentally anxious young children are at marked risk to develop SAD. Recent work in human and nonhuman primates has identified a distributed brain network that underlies early-life anxiety including: central nucleus of the amygdala, anterior hippocampus and orbitofrontal cortex. Moreover, studies in nonhuman primates demonstrate that alterations in this circuit are trait-like in that they are stable over time and across contexts. Importantly, the components of this circuit are differentially influenced by heritable and environmental factors and specific lesion studies demonstrate a causal role for multiple components of the circuit. Molecular studies in rodents and primates are pointing to disrupted neurodevelopmental and neuroplastic processes within critical components of the early-life dispositional anxiety neural circuit. The possibility of identifying an early-life at-risk phenotype, along with an understanding of its neurobiology, provides an unusual opportunity to conceptualize novel preventive intervention strategies aimed at reducing the suffering of anxious children and preventing them from developing further psychopathology. PMID:25157566

A translational neuroscience approach to understanding the development of social anxiety disorder and its pathophysiology.

PubMed

Fox, Andrew S; Kalin, Ned H

2014-11-01

This review brings together recent research from molecular, neural circuit, animal model, and human studies to help understand the neurodevelopmental mechanisms underlying social anxiety disorder. Social anxiety disorder is common and debilitating, and it often leads to further psychopathology. Numerous studies have demonstrated that extremely behaviorally inhibited and temperamentally anxious young children are at marked risk of developing social anxiety disorder. Recent work in human and nonhuman primates has identified a distributed brain network that underlies early-life anxiety including the central nucleus of the amygdala, the anterior hippocampus, and the orbitofrontal cortex. Studies in nonhuman primates have demonstrated that alterations in this circuit are trait-like in that they are stable over time and across contexts. Notably, the components of this circuit are differentially influenced by heritable and environmental factors, and specific lesion studies have demonstrated a causal role for multiple components of the circuit. Molecular studies in rodents and primates point to disrupted neurodevelopmental and neuroplastic processes within critical components of the early-life dispositional anxiety neural circuit. The possibility of identifying an early-life at-risk phenotype, along with an understanding of its neurobiology, provides an unusual opportunity to conceptualize novel preventive intervention strategies aimed at reducing the suffering of anxious children and preventing them from developing further psychopathology.

Visuospatial Asymmetries Arise from Differences in the Onset Time of Perceptual Evidence Accumulation.

PubMed

Newman, Daniel P; Loughnane, Gerard M; Kelly, Simon P; O'Connell, Redmond G; Bellgrove, Mark A

2017-03-22

Healthy subjects tend to exhibit a bias of visual attention whereby left hemifield stimuli are processed more quickly and accurately than stimuli appearing in the right hemifield. It has long been held that this phenomenon arises from the dominant role of the right cerebral hemisphere in regulating attention. However, methods that would enable more precise understanding of the mechanisms underpinning visuospatial bias have remained elusive. We sought to finely trace the temporal evolution of spatial biases by leveraging a novel bilateral dot motion detection paradigm. In combination with electroencephalography, this paradigm enables researchers to isolate discrete neural signals reflecting the key neural processes needed for making these detection decisions. These include signals for spatial attention, early target selection, evidence accumulation, and motor preparation. Using this method, we established that three key neural markers accounted for unique between-subject variation in visuospatial bias: hemispheric asymmetry in posterior α power measured before target onset, which is related to the distribution of preparatory attention across the visual field; asymmetry in the peak latency of the early N2c target-selection signal; and, finally, asymmetry in the onset time of the subsequent neural evidence-accumulation process with earlier onsets for left hemifield targets. Our development of a single paradigm to dissociate distinct processing components that track the temporal evolution of spatial biases not only advances our understanding of the neural mechanisms underpinning normal visuospatial attention bias, but may also in the future aid differential diagnoses in disorders of spatial attention. SIGNIFICANCE STATEMENT The significance of this research is twofold. First, it shows that individual differences in how humans direct their attention between left and right space reflects physiological differences in how early the brain starts to accumulate evidence for the existence of a visual target. Second, the novel methods developed here may have particular relevance to disorders of attention, such as unilateral spatial neglect. In the case of spatial neglect, pathological inattention to left space could have multiple underlying causes, including biased attention, impaired decision formation, or a motor deficit related to one side of space. Our development of a single paradigm to dissociate each of these components may aid in supporting more precise differential diagnosis in such heterogeneous disorders. Copyright © 2017 the authors 0270-6474/17/373378-08$15.00/0.

Development of Action Monitoring through Adolescence into Adulthood: ERP and Source Localization

ERIC Educational Resources Information Center

Ladouceur, Cecile D.; Dahl, Ronald E.; Carter, Cameron S.

2007-01-01

In this study we examined the development of three action monitoring event-related potentials (ERPs)--the error-related negativity (ERN/Ne), error positivity (P[subscript E]) and the N2--and estimated their neural sources. These ERPs were recorded during a flanker task in the following groups: early adolescents (mean age = 12 years), late…

Developmental Change in the ERP Responses to Familiar Faces in Toddlers with Autism Spectrum Disorders versus Typical Development

ERIC Educational Resources Information Center

Webb, Sara Jane; Jones, Emily J. H.; Merkle, Kristen; Venema, Kaitlin; Greenson, Jessica; Murias, Michael; Dawson, Geraldine

2011-01-01

Individuals with autism spectrum disorder (ASD) show differences in face processing abilities from early in development. To examine whether these differences reflect an atypical versus delayed developmental trajectory, neural responses to familiar and unfamiliar faces in twenty-four 18- to 47-month-old children with ASD were compared with…

Mapping the unconscious maintenance of a lost first language.

PubMed

Pierce, Lara J; Klein, Denise; Chen, Jen-Kai; Delcenserie, Audrey; Genesee, Fred

2014-12-02

Optimal periods during early development facilitate the formation of perceptual representations, laying the framework for future learning. A crucial question is whether such early representations are maintained in the brain over time without continued input. Using functional MRI, we show that internationally adopted (IA) children from China, exposed exclusively to French since adoption (mean age of adoption, 12.8 mo), maintained neural representations of their birth language despite functionally losing that language and having no conscious recollection of it. Their neural patterns during a Chinese lexical tone discrimination task matched those observed in Chinese/French bilinguals who have had continual exposure to Chinese since birth and differed from monolingual French speakers who had never been exposed to Chinese. They processed lexical tone as linguistically relevant, despite having no Chinese exposure for 12.6 y, on average, and no conscious recollection of that language. More specifically, IA participants recruited left superior temporal gyrus/planum temporale, matching the pattern observed in Chinese/French bilinguals. In contrast, French speakers who had never been exposed to Chinese did not recruit this region and instead activated right superior temporal gyrus. We show that neural representations are not overwritten and suggest a special status for language input obtained during the first year of development.

SMAD7 directly converts human embryonic stem cells to telencephalic fate by a default mechanism

PubMed Central

Ozair, Mohammad Zeeshan; Noggle, Scott; Warmflash, Aryeh; Krzyspiak, Joanna Ela; Brivanlou, Ali H.

2013-01-01

Human embryonic stem cells (hESCs) provide a valuable window into the dissection of the molecular circuitry underlying the early formation of the human forebrain. However, dissection of signaling events in forebrain development using current protocols is complicated by non-neural contamination and fluctuation of extrinsic influences. Here we show that SMAD7, a cell-intrinsic inhibitor of TGFβ signaling, is sufficient to directly convert pluripotent hESCs to an anterior neural fate. Time-course gene expression revealed down-regulation of MAPK components, and combining MEK1/2 inhibition with SMAD7-mediated TGFβ inhibition promoted telencephalic conversion. FGF-MEK and TGFβ-SMAD signaling maintain hESCs by promoting pluripotency genes and repressing neural genes. Our findings suggest that in the absence of these cues, pluripotent cells simply revert to a program of neural conversion. Hence the “primed” state of hESCs requires inhibition of the “default” state of neural fate acquisition. This has parallels in amphibians, suggesting an evolutionarily conserved mechanism. PMID:23034881

Pleiotrophin enhances PDGFB-induced gliomagenesis through increased proliferation of neural progenitor cells

PubMed Central

Zhang, Lei; Laaniste, Liisi; Jiang, Yiwen; Alafuzoff, Irina; Uhrbom, Lene; Dimberg, Anna

2016-01-01

Pleiotrophin (PTN) augments tumor growth by increasing proliferation of tumor cells and promoting vascular abnormalization, but its role in early gliomagenesis has not been evaluated. Through analysis of publically available datasets, we demonstrate that increased PTN mRNA expression is associated with amplification of chromosome 7, identified as one of the earliest steps in glioblastoma development. To elucidate the role of PTN in tumor initiation we employed the RCAS/tv-a model that allows glioma induction by RCAS-virus mediated expression of oncogenes in neural progenitor cells. Intracranial injection of RCAS-PTN did not induce glioma formation when administrated alone, but significantly enhanced RCAS-platelet derived growth factor (PDGF)B-induced gliomagenesis. PTN co-treatment augmented PDGFB-induced Akt activation in neural progenitor cells in vitro, and enhanced neural sphere size associated with increased proliferation. Our data indicates that PTN expression is associated with chromosome 7 gain, and that PTN enhances PDGFB-induced gliomagenesis by stimulating proliferation of neural progenitor cells. PMID:27806344

Pleiotrophin enhances PDGFB-induced gliomagenesis through increased proliferation of neural progenitor cells.

PubMed

Zhang, Lei; Laaniste, Liisi; Jiang, Yiwen; Alafuzoff, Irina; Uhrbom, Lene; Dimberg, Anna

2016-12-06

Pleiotrophin (PTN) augments tumor growth by increasing proliferation of tumor cells and promoting vascular abnormalization, but its role in early gliomagenesis has not been evaluated. Through analysis of publically available datasets, we demonstrate that increased PTN mRNA expression is associated with amplification of chromosome 7, identified as one of the earliest steps in glioblastoma development. To elucidate the role of PTN in tumor initiation we employed the RCAS/tv-a model that allows glioma induction by RCAS-virus mediated expression of oncogenes in neural progenitor cells. Intracranial injection of RCAS-PTN did not induce glioma formation when administrated alone, but significantly enhanced RCAS-platelet derived growth factor (PDGF)B-induced gliomagenesis. PTN co-treatment augmented PDGFB-induced Akt activation in neural progenitor cells in vitro, and enhanced neural sphere size associated with increased proliferation. Our data indicates that PTN expression is associated with chromosome 7 gain, and that PTN enhances PDGFB-induced gliomagenesis by stimulating proliferation of neural progenitor cells.

Maternal Depression and Warmth During Childhood Predict Age 20 Neural Response to Reward

PubMed Central

Morgan, Judith K.; Shaw, Daniel S.; Forbes, Erika E.

2014-01-01

Objective Early parenting experiences likely shape children’s brain development, with consequences potentially extending into adulthood. Parents’ affective disorders and expressions of positive affect could exert an influence on affect-related circuitry. The current study evaluated how maternal depression and maternal warmth assessed in early childhood and early adolescence were related to boys’ reward function during early adulthood. Method Participants were 120 boys at socioeconomic risk for emotional problems. Mothers’ history of depression during the child’s lifetime was measured when boys were 42 months old and 10/11 years old. Maternal warmth was observed during mother–child interactions at 18 and 24 months and at 10 and 11 years. Results Maternal warmth during early childhood was associated with less activation in the medial prefrontal cortex (mPFC) when anticipating and experiencing reward loss. Maternal warmth during early adolescence was associated with less activation in the mPFC when winning rewards and greater activation in the caudate when experiencing loss. The association between maternal warmth during early childhood and early adolescence and reward function in the striatum and mPFC was stronger for boys exposed to maternal depression relative to boys who were not. Conclusions The experience of warmth and affection from mothers may be a protective factor for reward function in boys exposed to maternal depression, possibly by engaging vulnerable neural reward systems through affiliation. PMID:24342390

Coordinating cell and tissue behavior during zebrafish neural tube morphogenesis.

PubMed

Araya, Claudio; Ward, Laura C; Girdler, Gemma C; Miranda, Miguel

2016-03-01

The development of a vertebrate neural epithelium with well-organized apico-basal polarity and a central lumen is essential for its proper function. However, how this polarity is established during embryonic development and the potential influence of surrounding signals and tissues on such organization has remained less understood. In recent years the combined superior transparency and genetics of the zebrafish embryo has allowed for in vivo visualization and quantification of the cellular and molecular dynamics that govern neural tube structure. Here, we discuss recent studies revealing how co-ordinated cell-cell interactions coupled with adjacent tissue dynamics are critical to regulate final neural tissue architecture. Furthermore, new findings show how the spatial regulation and timing of orientated cell division is key in defining precise lumen formation at the tissue midline. In addition, we compare zebrafish neurulation with that of amniotes and amphibians in an attempt to understand the conserved cellular mechanisms driving neurulation and resolve the apparent differences among animals. Zebrafish neurulation not only offers fundamental insights into early vertebrate brain development but also the opportunity to explore in vivo cell and tissue dynamics during complex three-dimensional animal morphogenesis. © 2015 Wiley Periodicals, Inc.

Effects of early life abuse differ across development: Infant social behavior deficits are followed by adolescent depressive-like behaviors mediated by the amygdala

PubMed Central

Raineki, Charlis; Cortés, Millie Rincón; Belnoue, Laure; Sullivan, Regina M.

2012-01-01

Abuse during early life, especially from the caregiver, increases vulnerability to develop later life psychopathologies such as depression. Although signs of depression are typically not expressed until later life, signs of dysfunctional social behavior have been found earlier. How infant abuse alters the trajectory of brain development to produce pathways to pathology is not completely understood. Here we address this question using two different but complementary rat models of early-life abuse from postnatal days (PN) 8–12: a naturalistic paradigm, where the mother is provided with insufficient bedding for nest building and a more controlled paradigm, where infants undergo olfactory classical conditioning. Amygdala neural assessment (c-Fos), as well as social behavior and forced swim tests were performed at preweaning (PN20) and adolescence (PN45). Our results show that both models of early life abuse induce deficits in social behavior, even during the preweaning period; however, depressive-like behaviors were observed only during adolescence. Adolescent depressive-like behavior corresponds with an increase in amygdala neural activity in response to forced swim test. A causal relationship between the amygdala and depressive-like behavior was suggested through amygdala temporary deactivation (muscimol infusions), which rescued the depressive-like behavior in the forced swim test. Our results indicate that social behavior deficits in infancy could serve as an early marker for later psychopathology. Moreover, the implication of the amygdala in the ontogeny of depressive-like behaviors in infant abused animals is an important step toward understanding the underlying mechanisms of later life mental disease associated with early-life abuse. PMID:22649253

Early Binocular Input Is Critical for Development of Audiovisual but Not Visuotactile Simultaneity Perception.

PubMed

Chen, Yi-Chuan; Lewis, Terri L; Shore, David I; Maurer, Daphne

2017-02-20

Temporal simultaneity provides an essential cue for integrating multisensory signals into a unified perception. Early visual deprivation, in both animals and humans, leads to abnormal neural responses to audiovisual signals in subcortical and cortical areas [1-5]. Behavioral deficits in integrating complex audiovisual stimuli in humans are also observed [6, 7]. It remains unclear whether early visual deprivation affects visuotactile perception similarly to audiovisual perception and whether the consequences for either pairing differ after monocular versus binocular deprivation [8-11]. Here, we evaluated the impact of early visual deprivation on the perception of simultaneity for audiovisual and visuotactile stimuli in humans. We tested patients born with dense cataracts in one or both eyes that blocked all patterned visual input until the cataractous lenses were removed and the affected eyes fitted with compensatory contact lenses (mean duration of deprivation = 4.4 months; range = 0.3-28.8 months). Both monocularly and binocularly deprived patients demonstrated lower precision in judging audiovisual simultaneity. However, qualitatively different outcomes were observed for the two patient groups: the performance of monocularly deprived patients matched that of young children at immature stages, whereas that of binocularly deprived patients did not match any stage in typical development. Surprisingly, patients performed normally in judging visuotactile simultaneity after either monocular or binocular deprivation. Therefore, early binocular input is necessary to develop normal neural substrates for simultaneity perception of visual and auditory events but not visual and tactile events. Copyright © 2017 Elsevier Ltd. All rights reserved.

To Stroop or Not to Stroop: Sex-Related Differences in Brain-Behavior Associations During Early Childhood

PubMed Central

Cuevas, Kimberly; Calkins, Susan D.; Bell, Martha Ann

2015-01-01

Executive functions (EFs) are linked with optimal cognitive and social-emotional development. Despite behavioral evidence of sex differences in early childhood EF, little is known about potential sex differences in corresponding brain-behavior associations. The present study examined changes in 4-year-olds’ 6–9 Hz EEG power in response to increased executive processing demands (i.e., “Stroop-like” vs. “non-Stroop” day-night tasks). Although there were no sex differences in task performance, an examination of multiple scalp electrode sites revealed that boys exhibited more widespread changes in EEG power as compared to girls. Further, multiple regression analyses controlling for maternal education and non-EF performance indicated that individual differences in boys’ and girls’ EF performance were associated with different frontal neural correlates (i.e., different frontal scalp sites and different measures of EEG power). These data reveal valuable information concerning sex differences in the neural systems underlying executive processing during early childhood. PMID:26681615

Prenatal neurogenesis in autism spectrum disorders

NASA Astrophysics Data System (ADS)

Kaushik, Gaurav; Zarbalis, Konstantinos

2016-03-01

An ever-increasing body of literature describes compelling evidence that a subset of young children on the autism spectrum show abnormal cerebral growth trajectories. In these cases, normal cerebral size at birth is followed by a period of abnormal growth and starting in late childhood often by regression compared to unaffected controls. Recent work has demonstrated an abnormal increase in the number of neurons of the prefrontal cortex suggesting that cerebral size increase in autism is driven by excess neuronal production. In addition, some affected children display patches of abnormal laminar positioning of cortical projection neurons. As both cortical projection neuron numbers and their correct layering within the developing cortex requires the undisturbed proliferation of neural progenitors, it appears that neural progenitors lie in the center of the autism pathology associated with early brain overgrowth. Consequently, autism spectrum disorders associated with cerebral enlargement should be viewed as birth defects of an early embryonic origin with profound implications for their early diagnosis, preventive strategies, and therapeutic intervention.

Neural decoding of collective wisdom with multi-brain computing.

PubMed

Eckstein, Miguel P; Das, Koel; Pham, Binh T; Peterson, Matthew F; Abbey, Craig K; Sy, Jocelyn L; Giesbrecht, Barry

2012-01-02

Group decisions and even aggregation of multiple opinions lead to greater decision accuracy, a phenomenon known as collective wisdom. Little is known about the neural basis of collective wisdom and whether its benefits arise in late decision stages or in early sensory coding. Here, we use electroencephalography and multi-brain computing with twenty humans making perceptual decisions to show that combining neural activity across brains increases decision accuracy paralleling the improvements shown by aggregating the observers' opinions. Although the largest gains result from an optimal linear combination of neural decision variables across brains, a simpler neural majority decision rule, ubiquitous in human behavior, results in substantial benefits. In contrast, an extreme neural response rule, akin to a group following the most extreme opinion, results in the least improvement with group size. Analyses controlling for number of electrodes and time-points while increasing number of brains demonstrate unique benefits arising from integrating neural activity across different brains. The benefits of multi-brain integration are present in neural activity as early as 200 ms after stimulus presentation in lateral occipital sites and no additional benefits arise in decision related neural activity. Sensory-related neural activity can predict collective choices reached by aggregating individual opinions, voting results, and decision confidence as accurately as neural activity related to decision components. Estimation of the potential for the collective to execute fast decisions by combining information across numerous brains, a strategy prevalent in many animals, shows large time-savings. Together, the findings suggest that for perceptual decisions the neural activity supporting collective wisdom and decisions arises in early sensory stages and that many properties of collective cognition are explainable by the neural coding of information across multiple brains. Finally, our methods highlight the potential of multi-brain computing as a technique to rapidly and in parallel gather increased information about the environment as well as to access collective perceptual/cognitive choices and mental states. Copyright © 2011 Elsevier Inc. All rights reserved.

A new mode of pancreatic islet innervation revealed by live imaging in zebrafish.

PubMed

Yang, Yu Hsuan Carol; Kawakami, Koichi; Stainier, Didier Yr

2018-06-19

Pancreatic islets are innervated by autonomic and sensory nerves that influence their function. Analyzing the innervation process should provide insight into the nerve-endocrine interactions and their roles in development and disease. Here, using in vivo time-lapse imaging and genetic analyses in zebrafish, we determined the events leading to islet innervation. Comparable neural density in the absence of vasculature indicates that it is dispensable for early pancreatic innervation. Neural crest cells are in close contact with endocrine cells early in development. We find these cells give rise to neurons that extend axons towards the islet as they surprisingly migrate away. Specific ablation of these neurons partly prevents other neurons from migrating away from the islet resulting in diminished innervation. Thus, our studies establish the zebrafish as a model to interrogate mechanisms of organ innervation, and reveal a novel mode of innervation whereby neurons establish connections with their targets before migrating away. © 2018, Yang et al.

Early Adverse Caregiving Experiences and Preschoolers' Current Attachment Affect Brain Responses during Facial Familiarity Processing: An ERP Study.

PubMed

Kungl, Melanie T; Bovenschen, Ina; Spangler, Gottfried

2017-01-01

When being placed into more benign environments like foster care, children from adverse rearing backgrounds are capable of forming attachment relationships to new caregivers within the first year of placement, while certain problematic social behaviors appear to be more persistent. Assuming that early averse experiences shape neural circuits underlying social behavior, neurophysiological studies on individual differences in early social-information processing have great informative value. More precisely, ERP studies have repeatedly shown face processing to be sensitive to experience especially regarding the caregiving background. However, studies on effects of early adverse caregiving experiences are restricted to children with a history of institutionalization. Also, no study has investigated effects of attachment security as a marker of the quality of the caregiver-child relationship. Thus, the current study asks how adverse caregiving experiences and attachment security to (new) caregivers affect early- and mid-latency ERPs sensitive to facial familiarity processing. Therefore, pre-school aged foster children during their second year within the foster home were compared to an age matched control group. Attachment was assessed using the AQS and neurophysiological data was collected during a passive viewing task presenting (foster) mother and stranger faces. Foster children were comparable to the control group with regard to attachment security. On a neurophysiological level, however, the foster group showed dampened N170 amplitudes for both face types. In both foster and control children, dampened N170 amplitudes were also found for stranger as compared to (foster) mother faces, and, for insecurely attached children as compared to securely attached children. This neural pattern may be viewed as a result of poorer social interactions earlier in life. Still, there was no effect on P1 amplitudes. Indicating heightened attentional processing, Nc amplitude responses to stranger faces were found to be enhanced in foster as compared to control children. Also, insecurely attached children allocated more attentional resources for the neural processing of mother faces. The study further confirms that early brain development is highly sensitive to the quality of caregiving. The findings are also relevant from a developmental perspective as miswiring of neural circuits may possibly play a critical role in children's psycho-social adjustment.

Intertrial auditory neural stability supports beat synchronization in preschoolers

PubMed Central

Carr, Kali Woodruff; Tierney, Adam; White-Schwoch, Travis; Kraus, Nina

2016-01-01

The ability to synchronize motor movements along with an auditory beat places stringent demands on the temporal processing and sensorimotor integration capabilities of the nervous system. Links between millisecond-level precision of auditory processing and the consistency of sensorimotor beat synchronization implicate fine auditory neural timing as a mechanism for forming stable internal representations of, and behavioral reactions to, sound. Here, for the first time, we demonstrate a systematic relationship between consistency of beat synchronization and trial-by-trial stability of subcortical speech processing in preschoolers (ages 3 and 4 years old). We conclude that beat synchronization might provide a useful window into millisecond-level neural precision for encoding sound in early childhood, when speech processing is especially important for language acquisition and development. PMID:26760457

Modelling collective cell migration of neural crest

PubMed Central

Szabó, András; Mayor, Roberto

2016-01-01

Collective cell migration has emerged in the recent decade as an important phenomenon in cell and developmental biology and can be defined as the coordinated and cooperative movement of groups of cells. Most studies concentrate on tightly connected epithelial tissues, even though collective migration does not require a constant physical contact. Movement of mesenchymal cells is more independent, making their emergent collective behaviour less intuitive and therefore lending importance to computational modelling. Here we focus on such modelling efforts that aim to understand the collective migration of neural crest cells, a mesenchymal embryonic population that migrates large distances as a group during early vertebrate development. By comparing different models of neural crest migration, we emphasize the similarity and complementary nature of these approaches and suggest a future direction for the field. The principles derived from neural crest modelling could aid understanding the collective migration of other mesenchymal cell types. PMID:27085004

Modelling collective cell migration of neural crest.

PubMed

Szabó, András; Mayor, Roberto

2016-10-01

Collective cell migration has emerged in the recent decade as an important phenomenon in cell and developmental biology and can be defined as the coordinated and cooperative movement of groups of cells. Most studies concentrate on tightly connected epithelial tissues, even though collective migration does not require a constant physical contact. Movement of mesenchymal cells is more independent, making their emergent collective behaviour less intuitive and therefore lending importance to computational modelling. Here we focus on such modelling efforts that aim to understand the collective migration of neural crest cells, a mesenchymal embryonic population that migrates large distances as a group during early vertebrate development. By comparing different models of neural crest migration, we emphasize the similarity and complementary nature of these approaches and suggest a future direction for the field. The principles derived from neural crest modelling could aid understanding the collective migration of other mesenchymal cell types. Copyright © 2016 Elsevier Ltd. All rights reserved.

Neural Systems of Positive Affect: Relevance to Understanding Child and Adolescent Depression?

PubMed Central

Forbes, Erika E.; Dahl, Ronald E.

2007-01-01

From an affective neuroscience perspective, the goal of achieving a deeper, more mechanistic understanding of the development of depression will require rigorous models that address the core underlying affective changes. Such an understanding will necessitate developing and testing hypotheses focusing on specific components of the complex neural systems involved in the regulation of emotion and motivation. In this paper, we illustrate these principles by describing one example of this type of approach: examining the role of disruptions in neural systems of positive affect relevant to Major Depressive Disorder in school-age children and adolescents. We begin by defining positive affect, proposing that positive affect can be distinguished from negative affect by its neurobehavioral features. We provide an overview of neural systems related to reward and positive affect, with a discussion of their potential involvement in depression. We describe a developmental psychopathology framework, addressing developmental issues that could play a role in the etiology and maintenance of early-onset depression. We review the literature on altered positive affect in depression, suggesting directions for future research. Finally, we discuss the treatment implications of this framework. PMID:16262994

Enteric nervous system specific deletion of Foxd3 disrupts glial cell differentiation and activates compensatory enteric progenitors.

PubMed

Mundell, Nathan A; Plank, Jennifer L; LeGrone, Alison W; Frist, Audrey Y; Zhu, Lei; Shin, Myung K; Southard-Smith, E Michelle; Labosky, Patricia A

2012-03-15

The enteric nervous system (ENS) arises from the coordinated migration, expansion and differentiation of vagal and sacral neural crest progenitor cells. During development, vagal neural crest cells enter the foregut and migrate in a rostro-to-caudal direction, colonizing the entire gastrointestinal tract and generating the majority of the ENS. Sacral neural crest contributes to a subset of enteric ganglia in the hindgut, colonizing the colon in a caudal-to-rostral wave. During this process, enteric neural crest-derived progenitors (ENPs) self-renew and begin expressing markers of neural and glial lineages as they populate the intestine. Our earlier work demonstrated that the transcription factor Foxd3 is required early in neural crest-derived progenitors for self-renewal, multipotency and establishment of multiple neural crest-derived cells and structures including the ENS. Here, we describe Foxd3 expression within the fetal and postnatal intestine: Foxd3 was strongly expressed in ENPs as they colonize the gastrointestinal tract and was progressively restricted to enteric glial cells. Using a novel Ednrb-iCre transgene to delete Foxd3 after vagal neural crest cells migrate into the midgut, we demonstrated a late temporal requirement for Foxd3 during ENS development. Lineage labeling of Ednrb-iCre expressing cells in Foxd3 mutant embryos revealed a reduction of ENPs throughout the gut and loss of Ednrb-iCre lineage cells in the distal colon. Although mutant mice were viable, defects in patterning and distribution of ENPs were associated with reduced proliferation and severe reduction of glial cells derived from the Ednrb-iCre lineage. Analyses of ENS-lineage and differentiation in mutant embryos suggested activation of a compensatory population of Foxd3-positive ENPs that did not express the Ednrb-iCre transgene. Our findings highlight the crucial roles played by Foxd3 during ENS development including progenitor proliferation, neural patterning, and glial differentiation and may help delineate distinct molecular programs controlling vagal versus sacral neural crest development. Copyright © 2012 Elsevier Inc. All rights reserved.

WDR62 Regulates Early Neural and Glial Progenitor Specification of Human Pluripotent Stem Cells

PubMed Central

Alshawaf, Abdullah J.; Antonic, Ana; Skafidas, Efstratios

2017-01-01

Mutations in WD40-repeat protein 62 (WDR62) are commonly associated with primary microcephaly and other developmental cortical malformations. We used human pluripotent stem cells (hPSC) to examine WDR62 function during human neural differentiation and model early stages of human corticogenesis. Neurospheres lacking WDR62 expression showed decreased expression of intermediate progenitor marker, TBR2, and also glial marker, S100β. In contrast, inhibition of c-Jun N-terminal kinase (JNK) signalling during hPSC neural differentiation induced upregulation of WDR62 with a corresponding increase in neural and glial progenitor markers, PAX6 and EAAT1, respectively. These findings may signify a role of WDR62 in specifying intermediate neural and glial progenitors during human pluripotent stem cell differentiation. PMID:28690640

Socioeconomic disadvantage and neural development from infancy through early childhood.

PubMed

Chin-Lun Hung, Galen; Hahn, Jill; Alamiri, Bibi; Buka, Stephen L; Goldstein, Jill M; Laird, Nan; Nelson, Charles A; Smoller, Jordan W; Gilman, Stephen E

2015-12-01

Early social experiences are believed to shape neurodevelopment, with potentially lifelong consequences. Yet minimal evidence exists regarding the role of the social environment on children's neural functioning, a core domain of neurodevelopment. We analysed data from 36 443 participants in the United States Collaborative Perinatal Project, a socioeconomically diverse pregnancy cohort conducted between 1959 and 1974. Study outcomes included: physician (neurologist or paediatrician)-rated neurological abnormality neonatally and thereafter at 4 months and 1 and 7 years; indicators of neurological hard signs and soft signs; and indicators of autonomic nervous system function. Children born to socioeconomically disadvantaged parents were more likely to exhibit neurological abnormalities at 4 months [odds ratio (OR) = 1.20; 95% confidence interval (CI) = 1.06, 1.37], 1 year (OR = 1.35; CI = 1.17, 1.56), and 7 years (OR = 1.67; CI = 1.48, 1.89), and more likely to exhibit neurological hard signs (OR = 1.39; CI = 1.10, 1.76), soft signs (OR = 1.26; CI = 1.09, 1.45) and autonomic nervous system dysfunctions at 7 years. Pregnancy and delivery complications, themselves associated with socioeconomic disadvantage, did not account for the higher risks of neurological abnormalities among disadvantaged children. Parental socioeconomic disadvantage was, independently from pregnancy and delivery complications, associated with abnormal child neural development during the first 7 years of life. These findings reinforce the importance of the early environment for neurodevelopment generally, and expand knowledge regarding the domains of neurodevelopment affected by environmental conditions. Further work is needed to determine the mechanisms linking socioeconomic disadvantage with children's neural functioning, the timing of such mechanisms and their potential reversibility. Published by Oxford University Press on behalf of the International Epidemiological Association 2015. This work is written by US Government employees and is in the public domain in the US.

Regulation of early Xenopus development by ErbB signaling

PubMed Central

Nie, Shuyi; Chang, Chenbei

2008-01-01

ErbB signaling has long been implicated in cancer formation and progression and is shown to regulate cell division, migration and death during tumorigenesis. The functions of the ErbB pathway during early vertebrate embryogenesis, however, are not well understood. Here we report characterization of ErbB activities during early frog development. Gain-of-function analyses show that EGFR, ErbB2 and ErbB4 induce ectopic tumor-like cell mass that contains increased numbers of mitotic cells. Both the muscle and the neural markers are expressed in these ectopic protrusions. ErbBs also induce mesodermal markers in ectodermal explants. Loss-of-function studies using carboxyl terminal-truncated dominant-negative ErbB receptors demonstrate that blocking ErbB signals leads to defective gastrulation movements and malformation of the embryonic axis with a reduction in the head structures in early frog embryos. These data, together with the observation that ErbBs are expressed early during frog embryogenesis, suggest that ErbBs regulate cell proliferation, movements and embryonic patterning during early Xenopus development. PMID:16258939

Autism as an adaptive common variant pathway for human brain development.

PubMed

Johnson, Mark H

2017-06-01

While research on focal perinatal lesions has provided evidence for recovery of function, much less is known about processes of brain adaptation resulting from mild but widespread disturbances to neural processing over the early years (such as alterations in synaptic efficiency). Rather than being viewed as a direct behavioral consequence of life-long neural dysfunction, I propose that autism is best viewed as the end result of engaging adaptive processes during a sensitive period. From this perspective, autism is not appropriately described as a disorder of neurodevelopment, but rather as an adaptive common variant pathway of human functional brain development. Copyright © 2017 The Author. Published by Elsevier Ltd.. All rights reserved.

The eye limits the brain's learning potential

PubMed Central

Zhou, Jiawei; Zhang, Yudong; Dai, Yun; Zhao, Haoxin; Liu, Rong; Hou, Fang; Liang, Bo; Hess, Robert F.; Zhou, Yifeng

2012-01-01

The concept of a critical period for visual development early in life during which sensory experience is essential to normal neural development is now well established. However recent evidence suggests that a limited degree of plasticity remains after this period and well into adulthood. Here, we ask the question, "what limits the degree of plasticity in adulthood?" Although this limit has been assumed to be due to neural factors, we show that the optical quality of the retinal image ultimately limits the brain potential for change. We correct the high-order aberrations (HOAs) normally present in the eye's optics using adaptive optics, and reveal a greater degree of neuronal plasticity than previously appreciated. PMID:22509464

Early changes in emotional processing as a marker of clinical response to SSRI treatment in depression.

PubMed

Godlewska, B R; Browning, M; Norbury, R; Cowen, P J; Harmer, C J

2016-11-22

Antidepressant treatment reduces behavioural and neural markers of negative emotional bias early in treatment and has been proposed as a mechanism of antidepressant drug action. Here, we provide a critical test of this hypothesis by assessing whether neural markers of early emotional processing changes predict later clinical response in depression. Thirty-five unmedicated patients with major depression took the selective serotonin re-uptake inhibitor (SSRI), escitalopram (10 mg), over 6 weeks, and were classified as responders (22 patients) versus non-responders (13 patients), based on at least a 50% reduction in symptoms by the end of treatment. The neural response to fearful and happy emotional facial expressions was assessed before and after 7 days of treatment using functional magnetic resonance imaging. Changes in the neural response to these facial cues after 7 days of escitalopram were compared in patients as a function of later clinical response. A sample of healthy controls was also assessed. At baseline, depressed patients showed greater activation to fear versus happy faces than controls in the insula and dorsal anterior cingulate. Depressed patients who went on to respond to the SSRI had a greater reduction in neural activity to fearful versus happy facial expressions after just 7 days of escitalopram across a network of regions including the anterior cingulate, insula, amygdala and thalamus. Mediation analysis confirmed that the direct effect of neural change on symptom response was not mediated by initial changes in depressive symptoms. These results support the hypothesis that early changes in emotional processing with antidepressant treatment are the basis of later clinical improvement. As such, early correction of negative bias may be a key mechanism of antidepressant drug action and a potentially useful predictor of therapeutic response.

The Physiology of Moral Maturity.

ERIC Educational Resources Information Center

Hemming, James

1991-01-01

Discusses an evolutionary approach to human morality. Emphasizes the rapid development of brain weight, neural circuits, and synaptic systems during early childhood. Concludes that the human brain has resources for generating responsible, caring behavior but must be nurtured and educated. Urges that moral training in a proper social climate be…

Human Maternal Brain Plasticity: Adaptation to Parenting

ERIC Educational Resources Information Center

Kim, Pilyoung

2016-01-01

New mothers undergo dynamic neural changes that support positive adaptation to parenting and the development of mother-infant relationships. In this article, I review important psychological adaptations that mothers experience during pregnancy and the early postpartum period. I then review evidence of structural and functional plasticity in human…

Localization of basic fibroblast growth factor binding sites in the chick embryonic neural retina.

PubMed

Cirillo, A; Arruti, C; Courtois, Y; Jeanny, J C

1990-12-01

We have investigated the localization of basic fibroblast growth factor (bFGF) binding sites during the development of the neural retina in the chick embryo. The specificity of the affinity of bFGF for its receptors was assessed by competition experiments with unlabelled growth factor or with heparin, as well as by heparitinase treatment of the samples. Two different types of binding sites were observed in the neural retina by light-microscopic autoradiography. The first type, localized mainly to basement membranes, was highly sensitive to heparitinase digestion and to competition with heparin. It was not developmentally regulated. The second type of binding site, resistant to heparin competition, appeared to be associated with retinal cells from the earliest stages studied (3-day-old embryo, stages 21-22 of Hamburger and Hamilton). Its distribution was found to vary during embryonic development, paralleling layering of the neural retina. Binding of bFGF to the latter sites was observed throughout the retinal neuroepithelium at early stages but displayed a distinct pattern at the time when the inner and outer plexiform layers were formed. During the development of the inner plexiform layer, a banded pattern of bFGF binding was observed. These bands, lying parallel to the vitreal surface, seemed to codistribute with the synaptic bands existing in the inner plexiform layer. The presence of intra-retinal bFGF binding sites whose distribution varies with embryonic development suggests a regulatory mechanism involving differential actions of bFGF on neural retinal cells.

Molecular stages of rapid and uniform neuralization of human embryonic stem cells.

PubMed

Bajpai, R; Coppola, G; Kaul, M; Talantova, M; Cimadamore, F; Nilbratt, M; Geschwind, D H; Lipton, S A; Terskikh, A V

2009-06-01

Insights into early human development are fundamental for our understanding of human biology. Efficient differentiation of human embryonic stem cells (hESCs) into neural precursor cells is critical for future cell-based therapies. Here, using defined conditions, we characterized a new method for rapid and uniform differentiation of hESCs into committed neural precursor cells (designated C-NPCs). Dynamic gene expression analysis identified several distinct stages of ESC neuralization and revealed functional modules of coregulated genes and pathways. The first wave of gene expression changes, likely corresponding to the transition through primitive ectoderm, started at day 3, preceding the formation of columnar neuroepithelial rosettes. The second wave started at day 5, coinciding with the formation of rosettes. The majority of C-NPCs were positive for both anterior and posterior markers of developing neuroepithelium. In culture, C-NPCs became electrophysiologically functional neurons; on transplantation into neonatal mouse brains, C-NPCs integrated into the cortex and olfactory bulb, acquiring appropriate neuronal morphologies and markers. Compared to rosette-NPCs,(1) C-NPCs exhibited limited in vitro expansion capacity and did not express potent oncogenes such as PLAG1 or RSPO3. Concordantly, we never detected tumors or excessive neural proliferation after transplantation of C-NPCs into mouse brains. In conclusion, our study provides a framework for future analysis of molecular signaling during ESC neuralization.

Relationship between ketamine-induced developmental neurotoxicity and NMDA receptor-mediated calcium influx in neural stem cell-derived neurons.

PubMed

Wang, Cheng; Liu, Fang; Patterson, Tucker A; Paule, Merle G; Slikker, William

2017-05-01

Ketamine, a noncompetitive NMDA receptor antagonist, is used as a general anesthetic and recent data suggest that general anesthetics can cause neuronal damage when exposure occurs during early brain development. To elucidate the underlying mechanisms associated with ketamine-induced neurotoxicity, stem cell-derived models, such as rodent neural stem cells harvested from rat fetuses and/or neural stem cells derived from human induced pluripotent stem cells (iPSC) can be utilized. Prolonged exposure of rodent neural stem cells to clinically-relevant concentrations of ketamine resulted in elevated NMDA receptor levels as indicated by NR1subunit over-expression in neurons. This was associated with enhanced damage in neurons. In contrast, the viability and proliferation rate of undifferentiated neural stem cells were not significantly affected after ketamine exposure. Calcium imaging data indicated that 50μM NMDA did not cause a significant influx of calcium in typical undifferentiated neural stem cells; however, it did produce an immediate elevation of intracellular free Ca 2+ [Ca 2+ ] i in differentiated neurons derived from the same neural stem cells. This paper reviews the literature on this subject and previous findings suggest that prolonged exposure of developing neurons to ketamine produces an increase in NMDA receptor expression (compensatory up-regulation) which allows for a higher/toxic influx of calcium into neurons once ketamine is removed from the system, leading to neuronal cell death likely due to elevated reactive oxygen species generation. The absence of functional NMDA receptors in cultured neural stem cells likely explains why clinically-relevant concentrations of ketamine did not affect undifferentiated neural stem cell viability. Published by Elsevier B.V.

An early role for sonic hedgehog from foregut endoderm in jaw development: ensuring neural crest cell survival.

PubMed

Brito, José M; Teillet, Marie-Aimée; Le Douarin, Nicole M

2006-08-01

We have investigated the role of Sonic hedgehog (Shh) in the development of facial structures by depriving chicken embryos of the most anterior sources of this morphogen, including the prechordal plate and the anterior ventral endoderm of the foregut, before the onset of neural crest cell (NCC) migration to the first branchial arch (BA1). The entire forehead, including the foregut endoderm, was removed at 5- to 10-somite stage (ss), which led to the absence of the lower jaw when the operation was performed before 7-ss. If the embryos were deprived of their forehead at 8- to 10-ss, they were later on endowed with a lower beak. In embryos that were operated on early, the NCCs migrated normally to BA1 but were subjected to massive apoptosis a few hours later. Cell death did not occur when forehead excision was performed at a later stage. In this case, onward expression of Shh in the ventral foregut endoderm extended caudally over the excision limit, and we hypothesized that absence of Shh production by the endoderm in embryos that were operated on early could be responsible for the NCC apoptosis and the failure of BA1 development. We thus provided exogenous Shh to the embryos that were operated on before 7-ss. In this case, the development of the lower jaw was rescued. Therefore, Shh derived from the ventral foregut endoderm ensures the survival of NCCs at a critical stage of BA1 development.

A historical survey of algorithms and hardware architectures for neural-inspired and neuromorphic computing applications

DOE PAGES

James, Conrad D.; Aimone, James B.; Miner, Nadine E.; ...

2017-01-04

In this study, biological neural networks continue to inspire new developments in algorithms and microelectronic hardware to solve challenging data processing and classification problems. Here in this research, we survey the history of neural-inspired and neuromorphic computing in order to examine the complex and intertwined trajectories of the mathematical theory and hardware developed in this field. Early research focused on adapting existing hardware to emulate the pattern recognition capabilities of living organisms. Contributions from psychologists, mathematicians, engineers, neuroscientists, and other professions were crucial to maturing the field from narrowly-tailored demonstrations to more generalizable systems capable of addressing difficult problem classesmore » such as object detection and speech recognition. Algorithms that leverage fundamental principles found in neuroscience such as hierarchical structure, temporal integration, and robustness to error have been developed, and some of these approaches are achieving world-leading performance on particular data classification tasks. Additionally, novel microelectronic hardware is being developed to perform logic and to serve as memory in neuromorphic computing systems with optimized system integration and improved energy efficiency. Key to such advancements was the incorporation of new discoveries in neuroscience research, the transition away from strict structural replication and towards the functional replication of neural systems, and the use of mathematical theory frameworks to guide algorithm and hardware developments.« less

A historical survey of algorithms and hardware architectures for neural-inspired and neuromorphic computing applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

James, Conrad D.; Aimone, James B.; Miner, Nadine E.

In this study, biological neural networks continue to inspire new developments in algorithms and microelectronic hardware to solve challenging data processing and classification problems. Here in this research, we survey the history of neural-inspired and neuromorphic computing in order to examine the complex and intertwined trajectories of the mathematical theory and hardware developed in this field. Early research focused on adapting existing hardware to emulate the pattern recognition capabilities of living organisms. Contributions from psychologists, mathematicians, engineers, neuroscientists, and other professions were crucial to maturing the field from narrowly-tailored demonstrations to more generalizable systems capable of addressing difficult problem classesmore » such as object detection and speech recognition. Algorithms that leverage fundamental principles found in neuroscience such as hierarchical structure, temporal integration, and robustness to error have been developed, and some of these approaches are achieving world-leading performance on particular data classification tasks. Additionally, novel microelectronic hardware is being developed to perform logic and to serve as memory in neuromorphic computing systems with optimized system integration and improved energy efficiency. Key to such advancements was the incorporation of new discoveries in neuroscience research, the transition away from strict structural replication and towards the functional replication of neural systems, and the use of mathematical theory frameworks to guide algorithm and hardware developments.« less

Id expression in amphioxus and lamprey highlights the role of gene cooption during neural crest evolution

NASA Technical Reports Server (NTRS)

Meulemans, Daniel; McCauley, David; Bronner-Fraser, Marianne

2003-01-01

Neural crest cells are unique to vertebrates and generate many of the adult structures that differentiate them from their closest invertebrate relatives, the cephalochordates. Id genes are robust markers of neural crest cells at all stages of development. We compared Id gene expression in amphioxus and lamprey to ask if cephalochordates deploy Id genes at the neural plate border and dorsal neural tube in a manner similar to vertebrates. Furthermore, we examined whether Id expression in these cells is a basal vertebrate trait or a derived feature of gnathostomes. We found that while expression of Id genes in the mesoderm and endoderm is conserved between amphioxus and vertebrates, expression in the lateral neural plate border and dorsal neural tube is a vertebrate novelty. Furthermore, expression of lamprey Id implies that recruitment of Id genes to these cells occurred very early in the vertebrate lineage. Based on expression in amphioxus we postulate that Id cooption conferred sensory cell progenitor-like properties upon the lateral neurectoderm, and pharyngeal mesoderm-like properties upon cranial neural crest. Amphioxus Id expression is also consistent with homology between the anterior neurectoderm of amphioxus and the presumptive placodal ectoderm of vertebrates. These observations support the idea that neural crest evolution was driven in large part by cooption of multipurpose transcriptional regulators from other tissues and cell types.

Testicular receptor 2, Nr2c1, is associated with stem cells in the developing olfactory epithelium and other cranial sensory and skeletal structures.

PubMed

Baker, Jennifer L; Wood, Bernard; Karpinski, Beverly A; LaMantia, Anthony-S; Maynard, Thomas M

2016-01-01

Comparative genomic analysis of the nuclear receptor family suggests that the testicular receptor 2, Nr2c1, undergoes positive selection in the human-chimpanzee clade based upon a significant increase in nonsynonymous compared to synonymous substitutions. Previous in situ analyses of Nr2c1 lacked the temporal range and spatial resolution necessary to characterize cellular expression of this gene from early to mid gestation, when many nuclear receptors are key regulators of tissue specific stem or progenitor cells. Thus, we asked whether Nr2c1 protein is associated with stem cell populations in the mid-gestation mouse embryo. Nr2c1 is robustly expressed in the developing olfactory epithelium. Its expression in the olfactory epithelium shifts from multiple progenitor classes at early stages to primarily transit amplifying cells later in olfactory epithelium development. In the early developing central nervous system, Nr2c1 is limited to the anterior telencephalon/olfactory bulb anlagen, coincident with Nestin-positive neuroepithelial stem cells. Nr2c1 is also seen in additional cranial sensory specializations including cells surrounding the mystacial vibrissae, the retinal pigment epithelium and Scarpa's ganglion. Nr2c1 was also detected in a subset of mesenchymal cells in developing teeth and cranial bones. The timing and distribution of embryonic expression suggests that Nr2c1 is primarily associated with the early genesis of mammalian cranial sensory neurons and craniofacial skeletal structures. Thus, Nr2c1 may be a candidate for mediating parallel adaptive changes in cranial neural sensory specializations such as the olfactory epithelium, retina and mystacial vibrissae and in non-neural craniofacial features including teeth. Copyright © 2015 Elsevier B.V. All rights reserved.

Auditory brainstem activity and development evoked by apical versus basal cochlear implant electrode stimulation in children.

PubMed

Gordon, K A; Papsin, B C; Harrison, R V

2007-08-01

The role of apical versus basal cochlear implant electrode stimulation on central auditory development was examined. We hypothesized that, in children with early onset deafness, auditory development evoked by basal electrode stimulation would differ from that evoked more apically. Responses of the auditory nerve and brainstem, evoked by an apical and a basal implant electrode, were measured over the first year of cochlear implant use in 50 children with early onset severe to profound deafness who used hearing aids prior to implantation. Responses at initial stimulation were of larger amplitude and shorter latency when evoked by the apical electrode. No significant effects of residual hearing or age were found on initial response amplitudes or latencies. With implant use, responses evoked by both electrodes showed decreases in wave and interwave latencies reflecting decreased neural conduction time through the brainstem. Apical versus basal differences persisted with implant experience with one exception; eIII-eV interlatency differences decreased with implant use. Acute stimulation shows prolongation of basally versus apically evoked auditory nerve and brainstem responses in children with severe to profound deafness. Interwave latencies reflecting neural conduction along the caudal and rostral portions of the brainstem decreased over the first year of implant use. Differences in neural conduction times evoked by apical versus basal electrode stimulation persisted in the caudal but not rostral brainstem. Activity-dependent changes of the auditory brainstem occur in response to both apical and basal cochlear implant electrode stimulation.

How Early Hormones Shape Gender Development

PubMed Central

Berenbaum, Sheri A.; Beltz, Adriene M.

2015-01-01

Many important psychological characteristics show sex differences, and are influenced by sex hormones at different developmental periods. We focus on the role of sex hormones in early development, particularly the differential effects of prenatal androgens on aspects of gender development. Increasing evidence confirms that prenatal androgens have facilitative effects on male-typed activity interests and engagement (including child toy preferences and adult careers), and spatial abilities, but relatively minimal effects on gender identity. Recent emphasis has been directed to the psychological mechanisms underlying these effects (including sex differences in propulsive movement, and androgen effects on interest in people versus things), and neural substrates of androgen effects (including regional brain volumes, and neural responses to mental rotation, sexually arousing stimuli, emotion, and reward). Ongoing and planned work is focused on understanding the ways in which hormones act jointly with the social environment across time to produce varying trajectories of gender development, and clarifying mechanisms by which androgens affect behaviors. Such work will be facilitated by applying lessons from other species, and by expanding methodology. Understanding hormonal influences on gender development enhances knowledge of psychological development generally, and has important implications for basic and applied questions, including sex differences in psychopathology, women’s underrepresentation in science and math, and clinical care of individuals with variations in gender expression. PMID:26688827

Developmental Bias for Number Words in the Intraparietal Sulcus

ERIC Educational Resources Information Center

Lussier, Courtney A.; Cantlon, Jessica F.

2017-01-01

Children and adults show behavioral evidence of psychological overlap between their early, non-symbolic numerical concepts and their later-developing symbolic numerical concepts. An open question is to what extent the common cognitive signatures observed between different numerical notations are coupled with physical overlap in neural processes.…

Relationship between concentrations of lutein and StARD3 among pediatric and geriatric human brain tissue

USDA-ARS?s Scientific Manuscript database

Lutein, a dietary carotenoid, selectively accumulates in human retina and brain. While many epidemiological studies show evidence of a relationship between lutein status and cognitive health, lutein's selective uptake in human brain tissue and its potential function in early neural development and c...

Emergence of order in visual system development.

PubMed Central

Shatz, C J

1996-01-01

Neural connections in the adult central nervous system are highly precise. In the visual system, retinal ganglion cells send their axons to target neurons in the lateral geniculate nucleus (LGN) in such a way that axons originating from the two eyes terminate in adjacent but nonoverlapping eye-specific layers. During development, however, inputs from the two eyes are intermixed, and the adult pattern emerges gradually as axons from the two eyes sort out to form the layers. Experiments indicate that the sorting-out process, even though it occurs in utero in higher mammals and always before vision, requires retinal ganglion cell signaling; blocking retinal ganglion cell action potentials with tetrodotoxin prevents the formation of the layers. These action potentials are endogenously generated by the ganglion cells, which fire spontaneously and synchronously with each other, generating "waves" of activity that travel across the retina. Calcium imaging of the retina shows that the ganglion cells undergo correlated calcium bursting to generate the waves and that amacrine cells also participate in the correlated activity patterns. Physiological recordings from LGN neurons in vitro indicate that the quasiperiodic activity generated by the retinal ganglion cells is transmitted across the synapse between ganglion cells to drive target LGN neurons. These observations suggest that (i) a neural circuit within the immature retina is responsible for generating specific spatiotemporal patterns of neural activity; (ii) spontaneous activity generated in the retina is propagated across central synapses; and (iii) even before the photoreceptors are present, nerve cell function is essential for correct wiring of the visual system during early development. Since spontaneously generated activity is known to be present elsewhere in the developing CNS, this process of activity-dependent wiring could be used throughout the nervous system to help refine early sets of neural connections into their highly precise adult patterns. Images Fig. 1 Fig. 4 PMID:8570602

Early-Life Stress Is Associated with Impairment in Cognitive Control in Adolescence: An fMRI Study

ERIC Educational Resources Information Center

Mueller, Sven C.; Maheu, Francoise S.; Dozier, Mary; Peloso, Elizabeth; Mandell, Darcy; Leibenluft, Ellen; Pine, Daniel S.; Ernst, Monique

2010-01-01

Early-life stress (ES) has been associated with diverse forms of psychopathology. Some investigators suggest that these associations reflect the effects of stress on the neural circuits that support cognitive control. However, very few prior studies have examined the associations between ES, cognitive control, and underlying neural architecture.…

Neural Bases of Language Switching in High and Early Proficient Bilinguals

ERIC Educational Resources Information Center

Garbin, G.; Costa, A.; Sanjuan, A.; Forn, C.; Rodriguez-Pujadas, A.; Ventura, N.; Belloch, V.; Hernandez, M.; Avila, C.

2011-01-01

The left inferior frontal cortex, the caudate and the anterior cingulate have been proposed as the neural origin of language switching, but most of the studies were conducted in low proficient bilinguals. In the present study, we investigated brain areas involved in language switching in a sample of 19 early, high-proficient Spanish-Catalan…

Temperament and Parenting Styles in Early Childhood Differentially Influence Neural Response to Peer Evaluation in Adolescence.

PubMed

Guyer, Amanda E; Jarcho, Johanna M; Pérez-Edgar, Koraly; Degnan, Kathryn A; Pine, Daniel S; Fox, Nathan A; Nelson, Eric E

2015-07-01

Behavioral inhibition (BI) is a temperament characterized by social reticence and withdrawal from unfamiliar or novel contexts and conveys risk for social anxiety disorder. Developmental outcomes associated with this temperament can be influenced by children's caregiving context. The convergence of a child's temperamental disposition and rearing environment is ultimately expressed at both the behavioral and neural levels in emotional and cognitive response patterns to social challenges. The present study used functional neuroimaging to assess the moderating effects of different parenting styles on neural response to peer rejection in two groups of adolescents characterized by their early childhood temperament (M(age) = 17.89 years, N = 39, 17 males, 22 females; 18 with BI; 21 without BI). The moderating effects of authoritarian and authoritative parenting styles were examined in three brain regions linked with social anxiety: ventrolateral prefrontal cortex (vlPFC), striatum, and amygdala. In youth characterized with BI in childhood, but not in those without BI, diminished responses to peer rejection in vlPFC were associated with higher levels of authoritarian parenting. In contrast, all youth showed decreased caudate response to peer rejection at higher levels of authoritative parenting. These findings indicate that BI in early life relates to greater neurobiological sensitivity to variance in parenting styles, particularly harsh parenting, in late adolescence. These results are discussed in relation to biopsychosocial models of development.

Temperament and Parenting Styles in Early Childhood Differentially Influence Neural Response to Peer Evaluation in Adolescence

PubMed Central

Guyer, Amanda E.; Jarcho, Johanna M.; Pérez-Edgar, Koraly; Degnan, Kathryn A.; Pine, Daniel S.; Fox, Nathan A.; Nelson, Eric E.

2015-01-01

Behavioral inhibition (BI) is a temperament characterized by social reticence and withdrawal from unfamiliar or novel contexts and conveys risk for social anxiety disorder. Developmental outcomes associated with this temperament can be influenced by children’s caregiving context. The convergence of a child’s temperamental disposition and rearing environment is ultimately expressed at both the behavioral and neural levels in emotional and cognitive response patterns to social challenges. The present study used functional neuroimaging to assess the moderating effects of different parenting styles on neural response to peer rejection in two groups of adolescents characterized by their early childhood temperament (Mage = 17.89 years, N= 39, 17 males, 22 females; 18 with BI; 21 without BI). The moderating effects of authoritarian and authoritative parenting styles were examined in three brain regions linked with social anxiety: ventrolateral prefrontal cortex (vlPFC), striatum, and amygdala. In youth characterized with BI in childhood, but not in those without BI, diminished responses to peer rejection in vlPFC were associated with higher levels of authoritarian parenting. In contrast, all youth showed decreased caudate response to peer rejection at higher levels of authoritative parenting. These findings indicate that BI in early life relates to greater neurobiological sensitivity to variance in parenting styles, particularly harsh parenting, in late adolescence. These results are discussed in relation to biopsychosocial models of development. PMID:25588884

A sleep state in Drosophila larvae required for neural stem cell proliferation

PubMed Central

Szuperak, Milan; Churgin, Matthew A; Borja, Austin J; Raizen, David M; Fang-Yen, Christopher

2018-01-01

Sleep during development is involved in refining brain circuitry, but a role for sleep in the earliest periods of nervous system elaboration, when neurons are first being born, has not been explored. Here we identify a sleep state in Drosophila larvae that coincides with a major wave of neurogenesis. Mechanisms controlling larval sleep are partially distinct from adult sleep: octopamine, the Drosophila analog of mammalian norepinephrine, is the major arousal neuromodulator in larvae, but dopamine is not required. Using real-time behavioral monitoring in a closed-loop sleep deprivation system, we find that sleep loss in larvae impairs cell division of neural progenitors. This work establishes a system uniquely suited for studying sleep during nascent periods, and demonstrates that sleep in early life regulates neural stem cell proliferation. PMID:29424688

Applying cognitive training to target executive functions during early development.

PubMed

Wass, Sam V

2015-01-01

Developmental psychopathology is increasingly recognizing the importance of distinguishing causal processes (i.e., the mechanisms that cause a disease) from developmental outcomes (i.e., the symptoms of the disorder as it is eventually diagnosed). Targeting causal processes early in disordered development may be more effective than waiting until outcomes are established and then trying to reverse the pathogenic process. In this review, I evaluate evidence suggesting that neural and behavioral plasticity may be greatest at very early stages of development. I also describe correlational evidence suggesting that, across a number of conditions, early emerging individual differences in attentional control and working memory may play a role in mediating later-developing differences in academic and other forms of learning. I review the currently small number of studies that applied direct and indirect cognitive training targeted at young individuals and discuss methodological challenges associated with targeting this age group. I also discuss a number of ways in which early, targeted cognitive training may be used to help us understand the developmental mechanisms subserving typical and atypical cognitive development.

Applying cognitive training to target executive functions during early development

PubMed Central

Wass, Sam V.

2015-01-01

Developmental psychopathology is increasingly recognizing the importance of distinguishing causal processes (i.e., the mechanisms that cause a disease) from developmental outcomes (i.e., the symptoms of the disorder as it is eventually diagnosed). Targeting causal processes early in disordered development may be more effective than waiting until outcomes are established and then trying to reverse the pathogenic process. In this review, I evaluate evidence suggesting that neural and behavioral plasticity may be greatest at very early stages of development. I also describe correlational evidence suggesting that, across a number of conditions, early emerging individual differences in attentional control and working memory may play a role in mediating later-developing differences in academic and other forms of learning. I review the currently small number of studies that applied direct and indirect cognitive training targeted at young individuals and discuss methodological challenges associated with targeting this age group. I also discuss a number of ways in which early, targeted cognitive training may be used to help us understand the developmental mechanisms subserving typical and atypical cognitive development. PMID:24511910

Serotonin-related pathways and developmental plasticity: relevance for psychiatric disorders

PubMed Central

Dayer, Alexandre

2014-01-01

Risk for adult psychiatric disorders is partially determined by early-life alterations occurring during neural circuit formation and maturation. In this perspective, recent data show that the serotonin system regulates key cellular processes involved in the construction of cortical circuits. Translational data for rodents indicate that early-life serotonin dysregulation leads to a wide range of behavioral alterations, ranging from stress-related phenotypes to social deficits. Studies in humans have revealed that serotonin-related genetic variants interact with early-life stress to regulate stress-induced cortisol responsiveness and activate the neural circuits involved in mood and anxiety disorders. Emerging data demonstrate that early-life adversity induces epigenetic modifications in serotonin-related genes. Finally, recent findings reveal that selective serotonin reuptake inhibitors can reinstate juvenile-like forms of neural plasticity, thus allowing the erasure of long-lasting fear memories. These approaches are providing new insights on the biological mechanisms and clinical application of antidepressants. PMID:24733969

Cell death in neural precursor cells and neurons before neurite formation prevents the emergence of abnormal neural structures in the Drosophila optic lobe.

PubMed

Hara, Yusuke; Sudo, Tatsuya; Togane, Yu; Akagawa, Hiromi; Tsujimura, Hidenobu

2018-04-01

Programmed cell death is a conserved strategy for neural development both in vertebrates and invertebrates and is recognized at various developmental stages in the brain from neurogenesis to adulthood. To understand the development of the central nervous system, it is essential to reveal not only molecular mechanisms but also the role of neural cell death (Pinto-Teixeira et al., 2016). To understand the role of cell death in neural development, we investigated the effect of inhibition of cell death on optic lobe development. Our data demonstrate that, in the optic lobe of Drosophila, cell death occurs in neural precursor cells and neurons before neurite formation and functions to prevent various developmental abnormalities. When neuronal cell death was inhibited by an effector caspase inhibitor, p35, multiple abnormal neuropil structures arose during optic lobe development-e.g., enlarged or fused neuropils, misrouted neurons and abnormal neurite lumps. Inhibition of cell death also induced morphogenetic defects in the lamina and medulla development-e.g., failures in the separation of the lamina and medulla cortices and the medulla rotation. These defects were reproduced in the mutant of an initiator caspase, dronc. If cell death was a mechanism for removing the abnormal neuropil structures, we would also expect to observe them in mutants defective for corpse clearance. However, they were not observed in these mutants. When dead cell-membranes were visualized with Apoliner, they were observed only in cortices and not in neuropils. These results suggest that the cell death occurs before mature neurite formation. Moreover, we found that inhibition of cell death induced ectopic neuroepithelial cells, neuroblasts and ganglion mother cells in late pupal stages, at sites where the outer and inner proliferation centers were located at earlier developmental stages. Caspase-3 activation was observed in the neuroepithelial cells and neuroblasts in the proliferation centers. These results indicate that cell death is required for elimination of the precursor cells composing the proliferation centers. This study substantiates an essential role of early neural cell death for ensuring normal development of the central nervous system. Copyright © 2018 Elsevier Inc. All rights reserved.

Preschool Externalizing Behavior Predicts Gender-Specific Variation in Adolescent Neural Structure

PubMed Central

Caldwell, Jessica Z. K.; Armstrong, Jeffrey M.; Hanson, Jamie L.; Sutterer, Matthew J.; Stodola, Diane E.; Koenigs, Michael; Kalin, Ned H.

2015-01-01

Dysfunction in the prefrontal cortex, amygdala, and hippocampus is believed to underlie the development of much psychopathology. However, to date only limited longitudinal data relate early behavior with neural structure later in life. Our objective was to examine the relationship of early life externalizing behavior with adolescent brain structure. We report here the first longitudinal study linking externalizing behavior during preschool to brain structure during adolescence. We examined the relationship of preschool externalizing behavior with amygdala, hippocampus, and prefrontal cortex volumes at age 15 years in a community sample of 76 adolescents followed longitudinally since their mothers’ pregnancy. A significant gender by externalizing behavior interaction revealed that males—but not females—with greater early childhood externalizing behavior had smaller amygdala volumes at adolescence (t = 2.33, p = .023). No significant results were found for the hippocampus or the prefrontal cortex. Greater early externalizing behavior also related to smaller volume of a cluster including the angular gyrus and tempoparietal junction across genders. Results were not attributable to the impact of preschool anxiety, preschool maternal stress, school-age internalizing or externalizing behaviors, or adolescent substance use. These findings demonstrate a novel, gender-specific relationship between early-childhood externalizing behavior and adolescent amygdala volume, as well as a cross-gender result for the angular gyrus and tempoparietal junction. PMID:25658357

Deep Recurrent Neural Networks for seizure detection and early seizure detection systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Talathi, S. S.

Epilepsy is common neurological diseases, affecting about 0.6-0.8 % of world population. Epileptic patients suffer from chronic unprovoked seizures, which can result in broad spectrum of debilitating medical and social consequences. Since seizures, in general, occur infrequently and are unpredictable, automated seizure detection systems are recommended to screen for seizures during long-term electroencephalogram (EEG) recordings. In addition, systems for early seizure detection can lead to the development of new types of intervention systems that are designed to control or shorten the duration of seizure events. In this article, we investigate the utility of recurrent neural networks (RNNs) in designing seizuremore » detection and early seizure detection systems. We propose a deep learning framework via the use of Gated Recurrent Unit (GRU) RNNs for seizure detection. We use publicly available data in order to evaluate our method and demonstrate very promising evaluation results with overall accuracy close to 100 %. We also systematically investigate the application of our method for early seizure warning systems. Our method can detect about 98% of seizure events within the first 5 seconds of the overall epileptic seizure duration.« less

Using a neural network approach and time series data from an international monitoring station in the Yellow Sea for modeling marine ecosystems.

PubMed

Zhang, Yingying; Wang, Juncheng; Vorontsov, A M; Hou, Guangli; Nikanorova, M N; Wang, Hongliang

2014-01-01

The international marine ecological safety monitoring demonstration station in the Yellow Sea was developed as a collaborative project between China and Russia. It is a nonprofit technical workstation designed as a facility for marine scientific research for public welfare. By undertaking long-term monitoring of the marine environment and automatic data collection, this station will provide valuable information for marine ecological protection and disaster prevention and reduction. The results of some initial research by scientists at the research station into predictive modeling of marine ecological environments and early warning are described in this paper. Marine ecological processes are influenced by many factors including hydrological and meteorological conditions, biological factors, and human activities. Consequently, it is very difficult to incorporate all these influences and their interactions in a deterministic or analysis model. A prediction model integrating a time series prediction approach with neural network nonlinear modeling is proposed for marine ecological parameters. The model explores the natural fluctuations in marine ecological parameters by learning from the latest observed data automatically, and then predicting future values of the parameter. The model is updated in a "rolling" fashion with new observed data from the monitoring station. Prediction experiments results showed that the neural network prediction model based on time series data is effective for marine ecological prediction and can be used for the development of early warning systems.

The neural signature of self-concept development in adolescence: The role of domain and valence distinctions.

PubMed

van der Cruijsen, R; Peters, S; van der Aar, L P E; Crone, E A

2017-11-22

Neuroimaging studies in adults showed that cortical midline regions including medial prefrontal cortex (mPFC) and posterior parietal cortex (PPC) are important in self-evaluations. The goals of this study were to investigate the contribution of these regions to self-evaluations in late childhood, adolescence, and early adulthood, and to examine whether these differed per domain (academic, physical and prosocial) and valence (positive versus negative). Also, we tested whether this activation changes across adolescence. For this purpose, participants between ages 11-21-years (N = 150) evaluated themselves on trait sentences in an fMRI session. Behaviorally, adolescents rated their academic traits less positively than children and young adults. The neural analyses showed that evaluating self-traits versus a control condition was associated with increased activity in mPFC (domain-general effect), and positive traits were associated with increased activity in ventral mPFC (valence effect). Self-related mPFC activation increased linearly with age, but only for evaluating physical traits. Furthermore, an adolescent-specific decrease in striatum activation for positive self traits was found. Finally, we found domain-specific neural activity for evaluating traits in physical (dorsolateral PFC, dorsal mPFC) and academic (PPC) domains. Together, these results highlight the importance of domain distinctions when studying self-concept development in late childhood, adolescence, and early adulthood. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Emergence of Adaptive Computation by Single Neurons in the Developing Cortex

PubMed Central

Famulare, Michael; Gjorgjieva, Julijana; Moody, William J.

2013-01-01

Adaptation is a fundamental computational motif in neural processing. To maintain stable perception in the face of rapidly shifting input, neural systems must extract relevant information from background fluctuations under many different contexts. Many neural systems are able to adjust their input–output properties such that an input's ability to trigger a response depends on the size of that input relative to its local statistical context. This “gain-scaling” strategy has been shown to be an efficient coding strategy. We report here that this property emerges during early development as an intrinsic property of single neurons in mouse sensorimotor cortex, coinciding with the disappearance of spontaneous waves of network activity, and can be modulated by changing the balance of spike-generating currents. Simultaneously, developing neurons move toward a common intrinsic operating point and a stable ratio of spike-generating currents. This developmental trajectory occurs in the absence of sensory input or spontaneous network activity. Through a combination of electrophysiology and modeling, we demonstrate that developing cortical neurons develop the ability to perform nearly perfect gain scaling by virtue of the maturing spike-generating currents alone. We use reduced single neuron models to identify the conditions for this property to hold. PMID:23884925

Copine1 regulates neural stem cell functions during brain development.

PubMed

Kim, Tae Hwan; Sung, Soo-Eun; Cheal Yoo, Jae; Park, Jae-Yong; Yi, Gwan-Su; Heo, Jun Young; Lee, Jae-Ran; Kim, Nam-Soon; Lee, Da Yong

2018-01-01

Copine 1 (CPNE1) is a well-known phospholipid binding protein in plasma membrane of various cell types. In brain cells, CPNE1 is closely associated with AKT signaling pathway, which is important for neural stem cell (NSC) functions during brain development. Here, we investigated the role of CPNE1 in the regulation of brain NSC functions during brain development and determined its underlying mechanism. In this study, abundant expression of CPNE1 was observed in neural lineage cells including NSCs and immature neurons in human. With mouse brain tissues in various developmental stages, we found that CPNE1 expression was higher at early embryonic stages compared to postnatal and adult stages. To model developing brain in vitro, we used primary NSCs derived from mouse embryonic hippocampus. Our in vitro study shows decreased proliferation and multi-lineage differentiation potential in CPNE1 deficient NSCs. Finally, we found that the deficiency of CPNE1 downregulated mTOR signaling in embryonic NSCs. These data demonstrate that CPNE1 plays a key role in the regulation of NSC functions through the activation of AKT-mTOR signaling pathway during brain development. Copyright © 2017 Elsevier Inc. All rights reserved.

Induced Pluripotent Stem Cells Generated from P0-Cre;Z/EG Transgenic Mice

PubMed Central

Ogawa, Yasuhiro; Eto, Akira; Miyake, Chisato; Tsuchida, Nana; Miyake, Haruka; Takaku, Yasuhiro; Hagiwara, Hiroaki; Oishi, Kazuhiko

2015-01-01

Neural crest (NC) cells are a migratory, multipotent cell population that arises at the neural plate border, and migrate from the dorsal neural tube to their target tissues, where they differentiate into various cell types. Abnormal development of NC cells can result in severe congenital birth defects. Because only a limited number of cells can be obtained from an embryo, mechanistic studies are difficult to perform with directly isolated NC cells. Protein zero (P0) is expressed by migrating NC cells during the early embryonic period. In the P0-Cre;Z/EG transgenic mouse, transient activation of the P0 promoter induces Cre-mediated recombination, indelibly tagging NC-derived cells with enhanced green fluorescent protein (EGFP). Induced pluripotent stem cell (iPSC) technology offers new opportunities for both mechanistic studies and development of stem cell-based therapies. Here, we report the generation of iPSCs from the P0-Cre;Z/EG mouse. P0-Cre;Z/EG mouse-derived iPSCs (P/G-iPSCs) exhibited pluripotent stem cell properties. In lineage-directed differentiation studies, P/G-iPSCs were efficiently differentiated along the neural lineage while expressing EGFP. These results suggest that P/G-iPSCs are useful to study NC development and NC-associated diseases. PMID:26382630

Induced Pluripotent Stem Cells Generated from P0-Cre;Z/EG Transgenic Mice.

PubMed

Ogawa, Yasuhiro; Eto, Akira; Miyake, Chisato; Tsuchida, Nana; Miyake, Haruka; Takaku, Yasuhiro; Hagiwara, Hiroaki; Oishi, Kazuhiko

2015-01-01

Neural crest (NC) cells are a migratory, multipotent cell population that arises at the neural plate border, and migrate from the dorsal neural tube to their target tissues, where they differentiate into various cell types. Abnormal development of NC cells can result in severe congenital birth defects. Because only a limited number of cells can be obtained from an embryo, mechanistic studies are difficult to perform with directly isolated NC cells. Protein zero (P0) is expressed by migrating NC cells during the early embryonic period. In the P0-Cre;Z/EG transgenic mouse, transient activation of the P0 promoter induces Cre-mediated recombination, indelibly tagging NC-derived cells with enhanced green fluorescent protein (EGFP). Induced pluripotent stem cell (iPSC) technology offers new opportunities for both mechanistic studies and development of stem cell-based therapies. Here, we report the generation of iPSCs from the P0-Cre;Z/EG mouse. P0-Cre;Z/EG mouse-derived iPSCs (P/G-iPSCs) exhibited pluripotent stem cell properties. In lineage-directed differentiation studies, P/G-iPSCs were efficiently differentiated along the neural lineage while expressing EGFP. These results suggest that P/G-iPSCs are useful to study NC development and NC-associated diseases.

Expression profiles of the Gα subunits during Xenopus tropicalis embryonic development.

PubMed

Fuentealba, Jaime; Toro-Tapia, Gabriela; Rodriguez, Marion; Arriagada, Cecilia; Maureira, Alejandro; Beyer, Andrea; Villaseca, Soraya; Leal, Juan I; Hinrichs, Maria V; Olate, Juan; Caprile, Teresa; Torrejón, Marcela

2016-09-01

Heterotrimeric G protein signaling plays major roles during different cellular events. However, there is a limited understanding of the molecular mechanisms underlying G protein control during embryogenesis. G proteins are highly conserved and can be grouped into four subfamilies according to sequence homology and function. To further studies on G protein function during embryogenesis, the present analysis identified four Gα subunits representative of the different subfamilies and determined their spatiotemporal expression patterns during Xenopus tropicalis embryogenesis. Each of the Gα subunit transcripts was maternally and zygotically expressed, and, as development progressed, dynamic expression patterns were observed. In the early developmental stages, the Gα subunits were expressed in the animal hemisphere and dorsal marginal zone. While expression was observed at the somite boundaries, in vascular structures, in the eye, and in the otic vesicle during the later stages, expression was mainly found in neural tissues, such as the neural tube and, especially, in the cephalic vesicles, neural crest region, and neural crest-derived structures. Together, these results support the pleiotropism and complexity of G protein subfamily functions in different cellular events. The present study constitutes the most comprehensive description to date of the spatiotemporal expression patterns of Gα subunits during vertebrate development. Copyright © 2016 Elsevier B.V. All rights reserved.

Neuroimaging, a new tool for investigating the effects of early diet on cognitive and brain development

PubMed Central

Isaacs, Elizabeth B.

2013-01-01

Nutrition is crucial to the initial development of the central nervous system (CNS), and then to its maintenance, because both depend on dietary intake to supply the elements required to develop and fuel the system. Diet in early life is often seen in the context of “programming” where a stimulus occurring during a vulnerable period can have long-lasting or even lifetime effects on some aspect of the organism's structure or function. Nutrition was first shown to be a programming stimulus for growth, and then for cognitive behavior, in animal studies that were able to employ methods that allowed the demonstration of neural effects of early nutrition. Such research raised the question of whether nutrition could also programme cognition/brain structure in humans. Initial studies of cognitive effects were observational, usually conducted in developing countries where the presence of confounding factors made it difficult to interpret the role of nutrition in the cognitive deficits that were seen. Attributing causality to nutrition required randomized controlled trials (RCTs) and these, often in developed countries, started to appear around 30 years ago. Most demonstrated convincingly that early nutrition could affect subsequent cognition. Until the advent of neuroimaging techniques that allowed in vivo examination of the brain, however, we could determine very little about the neural effects of early diet in humans. The combination of well-designed trials with neuroimaging tools means that we are now able to pose and answer questions that would have seemed impossible only recently. This review discusses various neuroimaging methods that are suitable for use in nutrition studies, while pointing out some of the limitations that they may have. The existing literature is small, but examples of studies that have used these methods are presented. Finally, some considerations that have arisen from previous studies, as well as suggestions for future research, are discussed. PMID:23964224

FoxA4 favours notochord formation by inhibiting contiguous mesodermal fates and restricts anterior neural development in Xenopus embryos.

PubMed

Murgan, Sabrina; Castro Colabianchi, Aitana Manuela; Monti, Renato José; Boyadjián López, Laura Elena; Aguirre, Cecilia E; Stivala, Ernesto González; Carrasco, Andrés E; López, Silvia L

2014-01-01

In vertebrates, the embryonic dorsal midline is a crucial signalling centre that patterns the surrounding tissues during development. Members of the FoxA subfamily of transcription factors are expressed in the structures that compose this centre. Foxa2 is essential for dorsal midline development in mammals, since knock-out mouse embryos lack a definitive node, notochord and floor plate. The related gene foxA4 is only present in amphibians. Expression begins in the blastula -chordin and -noggin expressing centre (BCNE) and is later restricted to the dorsal midline derivatives of the Spemann's organiser. It was suggested that the early functions of mammalian foxa2 are carried out by foxA4 in frogs, but functional experiments were needed to test this hypothesis. Here, we show that some important dorsal midline functions of mammalian foxa2 are exerted by foxA4 in Xenopus. We provide new evidence that the latter prevents the respecification of dorsal midline precursors towards contiguous fates, inhibiting prechordal and paraxial mesoderm development in favour of the notochord. In addition, we show that foxA4 is required for the correct regionalisation and maintenance of the central nervous system. FoxA4 participates in constraining the prospective rostral forebrain territory during neural specification and is necessary for the correct segregation of the most anterior ectodermal derivatives, such as the cement gland and the pituitary anlagen. Moreover, the early expression of foxA4 in the BCNE (which contains precursors of the whole forebrain and most of the midbrain and hindbrain) is directly required to restrict anterior neural development.

Abnormal neural precursor cell regulation in the early postnatal Fragile X mouse hippocampus.

PubMed

Sourial, Mary; Doering, Laurie C

2017-07-01

The regulation of neural precursor cells (NPCs) is indispensable for a properly functioning brain. Abnormalities in NPC proliferation, differentiation, survival, or integration have been linked to various neurological diseases including Fragile X syndrome. Yet, no studies have examined NPCs from the early postnatal Fragile X mouse hippocampus despite the importance of this developmental time point, which marks the highest expression level of FMRP, the protein missing in Fragile X, in the rodent hippocampus and is when hippocampal NPCs have migrated to the dentate gyrus (DG) to give rise to lifelong neurogenesis. In this study, we examined NPCs from the early postnatal hippocampus and DG of Fragile X mice (Fmr1-KO). Immunocytochemistry on neurospheres showed increased Nestin expression and decreased Ki67 expression, which collectively indicated aberrant NPC biology. Intriguingly, flow cytometric analysis of the expression of the antigens CD15, CD24, CD133, GLAST, and PSA-NCAM showed a decreased proportion of neural stem cells (GLAST + CD15 + CD133 + ) and an increased proportion of neuroblasts (PSA-NCAM + CD15 + ) in the DG of P7 Fmr1-KO mice. This was mirrored by lower expression levels of Nestin and the mitotic marker phospho-histone H3 in vivo in the P9 hippocampus, as well as a decreased proportion of cells in the G 2 /M phases of the P7 DG. Thus, the absence of FMRP leads to fewer actively cycling NPCs, coinciding with a decrease in neural stem cells and an increase in neuroblasts. Together, these results show the importance of FMRP in the developing hippocampal formation and suggest abnormalities in cell cycle regulation in Fragile X. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Neural correlates of audiotactile phonetic processing in early-blind readers: an fMRI study.

PubMed

Pishnamazi, Morteza; Nojaba, Yasaman; Ganjgahi, Habib; Amousoltani, Asie; Oghabian, Mohammad Ali

2016-05-01

Reading is a multisensory function that relies on arbitrary associations between auditory speech sounds and symbols from a second modality. Studies of bimodal phonetic perception have mostly investigated the integration of visual letters and speech sounds. Blind readers perform an analogous task by using tactile Braille letters instead of visual letters. The neural underpinnings of audiotactile phonetic processing have not been studied before. We used functional magnetic resonance imaging to reveal the neural correlates of audiotactile phonetic processing in 16 early-blind Braille readers. Braille letters and corresponding speech sounds were presented in unimodal, and congruent/incongruent bimodal configurations. We also used a behavioral task to measure the speed of blind readers in identifying letters presented via tactile and/or auditory modalities. Reaction times for tactile stimuli were faster. The reaction times for bimodal stimuli were equal to those for the slower auditory-only stimuli. fMRI analyses revealed the convergence of unimodal auditory and unimodal tactile responses in areas of the right precentral gyrus and bilateral crus I of the cerebellum. The left and right planum temporale fulfilled the 'max criterion' for bimodal integration, but activities of these areas were not sensitive to the phonetical congruency between sounds and Braille letters. Nevertheless, congruency effects were found in regions of frontal lobe and cerebellum. Our findings suggest that, unlike sighted readers who are assumed to have amodal phonetic representations, blind readers probably process letters and sounds separately. We discuss that this distinction might be due to mal-development of multisensory neural circuits in early blinds or it might be due to inherent differences between Braille and print reading mechanisms.

Anatomically ordered tapping interferes more with one-digit addition than two-digit addition: a dual-task fMRI study.

PubMed

Soylu, Firat; Newman, Sharlene D

2016-02-01

Fingers are used as canonical representations for numbers across cultures. In previous imaging studies, it was shown that arithmetic processing activates neural resources that are known to participate in finger movements. Additionally, in one dual-task study, it was shown that anatomically ordered finger tapping disrupts addition and subtraction more than multiplication, possibly due to a long-lasting effect of early finger counting experiences on the neural correlates and organization of addition and subtraction processes. How arithmetic task difficulty and tapping complexity affect the concurrent performance is still unclear. If early finger counting experiences have bearing on the neural correlates of arithmetic in adults, then one would expect anatomically and non-anatomically ordered tapping to have different interference effects, given that finger counting is usually anatomically ordered. To unravel these issues, we studied how (1) arithmetic task difficulty and (2) the complexity of the finger tapping sequence (anatomical vs. non-anatomical ordering) affect concurrent performance and use of key neural circuits using a mixed block/event-related dual-task fMRI design with adult participants. The results suggest that complexity of the tapping sequence modulates interference on addition, and that one-digit addition (fact retrieval), compared to two-digit addition (calculation), is more affected from anatomically ordered tapping. The region-of-interest analysis showed higher left angular gyrus BOLD response for one-digit compared to two-digit addition, and in no-tapping conditions than dual tapping conditions. The results support a specific association between addition fact retrieval and anatomically ordered finger movements in adults, possibly due to finger counting strategies that deploy anatomically ordered finger movements early in the development.

Clonal and molecular analysis of the prospective anterior neural boundary in the mouse embryo

PubMed Central

Cajal, Marieke; Lawson, Kirstie A.; Hill, Bill; Moreau, Anne; Rao, Jianguo; Ross, Allyson; Collignon, Jérôme; Camus, Anne

2012-01-01

In the mouse embryo the anterior ectoderm undergoes extensive growth and morphogenesis to form the forebrain and cephalic non-neural ectoderm. We traced descendants of single ectoderm cells to study cell fate choice and cell behaviour at late gastrulation. In addition, we provide a comprehensive spatiotemporal atlas of anterior gene expression at stages crucial for anterior ectoderm regionalisation and neural plate formation. Our results show that, at late gastrulation stage, expression patterns of anterior ectoderm genes overlap significantly and correlate with areas of distinct prospective fates but do not define lineages. The fate map delineates a rostral limit to forebrain contribution. However, no early subdivision of the presumptive forebrain territory can be detected. Lineage analysis at single-cell resolution revealed that precursors of the anterior neural ridge (ANR), a signalling centre involved in forebrain development and patterning, are clonally related to neural ectoderm. The prospective ANR and the forebrain neuroectoderm arise from cells scattered within the same broad area of anterior ectoderm. This study establishes that although the segregation between non-neural and neural precursors in the anterior midline ectoderm is not complete at late gastrulation stage, this tissue already harbours elements of regionalisation that prefigure the later organisation of the head. PMID:22186731

[Osteological development of the vertebral column and caudal complex of Lujanus guttatus (Perciformes: Lutjanidae) larvae under rearing conditions].

PubMed

Rodríguez-Ibarra, Luz Estela; Abdo-de la Parra, María Isabel; Aguilar-Zárate, Gabriela; Valasco-Blanco, Gabriela; Ibarra-Castro, Leonardo

2015-03-01

The spotted rose snapper (Lutjanus guttatus) is an important commercial species in Mexico with good culture potential. The osteological study at early stages in this species is an important tool to confirm normal bone structure and for the detection of malformations that may occur during early development. This study was carried out in order to evaluate and describe the normal osteological development of the vertebral column and caudal complex of this species grown under controlled conditions. For this, a total of 540 larvae of L. guttatus, between 2.1 and 17.5 mm of total length (TL), were cultured during 36 days; culture conditions were 28 degrees C, 5.74 mg/L oxygen and 32.2 ups salinity with standard feeding rates. To detect growth changes, a sample of 15 organisms was daily taken from day one until day 36 of post-hatch (DPH). Samples were processed following standard techniques of clearing, and cartilage (alcian blue) and bone staining (alizarin red). Results showed that the vertebral column is composed of ten vertebrae in the abdominal region, and 14 vertebrae including the urostyle in the caudal region. The development of the axial skeleton starts with the neural arches and haemal arches at 3.8 mm TL. Caudal elements such as the hypurals and parahypural began to develop at 4.1 mm TL. Pre-flexion and flexion of the notochord and the formation of all hypurals were observed between 5.3 and 5.8 mm TL. Ossification of the vertebrae in the abdominal region and in some neural arches initiated at 9.5mm TL. In the caudal region, all the neural and haemal arches ossified at 10.2 mm TL. All the abdominal vertebrae and their respective neural arches and parapophyses ossified at 11.2 mm TL, while the elements of the caudal complex that ossified were the hypurals, parahypurals and modified haemal spines. All caudal fm rays, 12 neural spines and 3 haemal arches were ossified by 15.5 mm. The complete ossification process of this specie under laboratory culture conditions was observed when larvae reached 17.3 mm TL on 36 DPH. Detailed analysis of the osteological structures will allow a reference description to evaluate and detect malformations that may occur during the larval culture of the spotted rose snapper.

Toward a conceptual framework for early brain and behavior development in autism

PubMed Central

Piven, J; Elison, J T; Zylka, M J

2017-01-01

Studies of infant siblings of older autistic probands, who are at elevated risk for autism, have demonstrated that the defining features of autism are not present in the first year of life but emerge late in the first and into the second year. A recent longitudinal neuroimaging study of high-risk siblings revealed a specific pattern of brain development in infants later diagnosed with autism, characterized by cortical surface area hyper-expansion in the first year followed by brain volume overgrowth in the second year that is associated with the emergence of autistic social deficits. Together with new observations from genetically defined autism risk alleles and rodent model, these findings suggest a conceptual framework for the early, post-natal development of autism. This framework postulates that an increase in the proliferation of neural progenitor cells and hyper-expansion of cortical surface area in the first year, occurring during a pre-symptomatic period characterized by disrupted sensorimotor and attentional experience, leads to altered experience-dependent neuronal development and decreased elimination of neuronal processes. This process is linked to brain volume overgrowth and disruption of the refinement of neural circuit connections and is associated with the emergence of autistic social deficits in the second year of life. A better understanding of the timing of developmental brain and behavior mechanisms in autism during infancy, a period which precedes the emergence of the defining features of this disorder, will likely have important implications for designing rational approaches to early intervention. PMID:28937691

A neural based intelligent flight control system for the NASA F-15 flight research aircraft

NASA Technical Reports Server (NTRS)

Urnes, James M.; Hoy, Stephen E.; Ladage, Robert N.; Stewart, James

1993-01-01

A flight control concept that can identify aircraft stability properties and continually optimize the aircraft flying qualities has been developed by McDonnell Aircraft Company under a contract with the NASA-Dryden Flight Research Facility. This flight concept, termed the Intelligent Flight Control System, utilizes Neural Network technology to identify the host aircraft stability and control properties during flight, and use this information to design on-line the control system feedback gains to provide continuous optimum flight response. This self-repairing capability can provide high performance flight maneuvering response throughout large flight envelopes, such as needed for the National Aerospace Plane. Moreover, achieving this response early in the vehicle's development schedule will save cost.

An RNA-binding protein, Qki5, regulates embryonic neural stem cells through pre-mRNA processing in cell adhesion signaling.

PubMed

Hayakawa-Yano, Yoshika; Suyama, Satoshi; Nogami, Masahiro; Yugami, Masato; Koya, Ikuko; Furukawa, Takako; Zhou, Li; Abe, Manabu; Sakimura, Kenji; Takebayashi, Hirohide; Nakanishi, Atsushi; Okano, Hideyuki; Yano, Masato

2017-09-15

Cell type-specific transcriptomes are enabled by the action of multiple regulators, which are frequently expressed within restricted tissue regions. In the present study, we identify one such regulator, Quaking 5 (Qki5), as an RNA-binding protein (RNABP) that is expressed in early embryonic neural stem cells and subsequently down-regulated during neurogenesis. mRNA sequencing analysis in neural stem cell culture indicates that Qki proteins play supporting roles in the neural stem cell transcriptome and various forms of mRNA processing that may result from regionally restricted expression and subcellular localization. Also, our in utero electroporation gain-of-function study suggests that the nuclear-type Qki isoform Qki5 supports the neural stem cell state. We next performed in vivo transcriptome-wide protein-RNA interaction mapping to search for direct targets of Qki5 and elucidate how Qki5 regulates neural stem cell function. Combined with our transcriptome analysis, this mapping analysis yielded a bona fide map of Qki5-RNA interaction at single-nucleotide resolution, the identification of 892 Qki5 direct target genes, and an accurate Qki5-dependent alternative splicing rule in the developing brain. Last, our target gene list provides the first compelling evidence that Qki5 is associated with specific biological events; namely, cell-cell adhesion. This prediction was confirmed by histological analysis of mice in which Qki proteins were genetically ablated, which revealed disruption of the apical surface of the lateral wall in the developing brain. These data collectively indicate that Qki5 regulates communication between neural stem cells by mediating numerous RNA processing events and suggest new links between splicing regulation and neural stem cell states. © 2017 Hayakawa-Yano et al.; Published by Cold Spring Harbor Laboratory Press.

FGF-2 signal promotes proliferation of cerebellar progenitor cells and their oligodendrocytic differentiation at early postnatal stage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Naruse, Masae; Shibasaki, Koji; Ishizaki, Yasuki, E-mail: yasukiishizaki@gunma-u.ac.jp

The origins and developmental regulation of cerebellar oligodendrocytes are largely unknown, although some hypotheses of embryonic origins have been suggested. Neural stem cells exist in the white matter of postnatal cerebellum, but it is unclear whether these neural stem cells generate oligodendrocytes at postnatal stages. We previously showed that cerebellar progenitor cells, including neural stem cells, widely express CD44 at around postnatal day 3. In the present study, we showed that CD44-positive cells prepared from the postnatal day 3 cerebellum gave rise to neurospheres, while CD44-negative cells prepared from the same cerebellum did not. These neurospheres differentiated mainly into oligodendrocytesmore » and astrocytes, suggesting that CD44-positive neural stem/progenitor cells might generate oligodendrocytes in postnatal cerebellum. We cultured CD44-positive cells from the postnatal day 3 cerebellum in the presence of signaling molecules known as mitogens or inductive differentiation factors for oligodendrocyte progenitor cells. Of these, only FGF-2 promoted survival and proliferation of CD44-positive cells, and these cells differentiated into O4+ oligodendrocytes. Furthermore, we examined the effect of FGF-2 on cerebellar oligodendrocyte development ex vivo. FGF-2 enhanced proliferation of oligodendrocyte progenitor cells and increased the number of O4+ and CC1+ oligodendrocytes in slice cultures. These results suggest that CD44-positive cells might be a source of cerebellar oligodendrocytes and that FGF-2 plays important roles in their development at an early postnatal stage. - Highlights: • CD44 is expressed in cerebellar neural stem/progenitor cells at postnatal day 3 (P3). • FGF-2 promoted proliferation of CD44-positive progenitor cells from P3 cerebellum. • FGF-2 promoted oligodendrocytic differentiation of CD44-positive progenitor cells. • FGF-2 increased the number of oligodendrocytes in P3 cerebellar slice culture.« less

Function of the two Xenopus smad4s in early frog development.

PubMed

Chang, Chenbei; Brivanlou, Ali H; Harland, Richard M

2006-10-13

Signals from the transforming growth factor beta family members are transmitted in the cell through specific receptor-activated Smads and a common partner Smad4. Two Smad4 genes (alpha and beta/10, or smad4 and smad4.2) have been isolated from Xenopus, and conflicting data are reported for Smad4beta/10 actions in mesodermal and neural induction. To further understand the functions of the Smad4s in early frog development, we analyzed their activities in detail. We report that Smad10 is a mutant form of Smad4beta that harbors a missense mutation of a conserved arginine to histidine in the MH1 domain. The mutation results in enhanced association of Smad10 with the nuclear transcription corepressor Ski and leads to its neural inducing activity through inhibition of bone morphogenetic protein (BMP) signaling. In contrast to Smad10, both Smad4alpha and Smad4beta enhanced BMP signals in ectodermal explants. Using antisense morpholino oligonucleotides (MOs) to knockdown endogenous Smad4 protein levels, we discovered that Smad4beta was required for both activin- and BMP-mediated mesodermal induction in animal caps, whereas Smad4alpha affected only the BMP signals. Neither Smad4 was involved directly in neural induction. Expression of Smad4beta-MO in early frog embryos resulted in reduction of mesodermal markers and defects in axial structures, which were rescued by either Smad4alpha or Smad4beta. Smad4alpha-MO induced only minor deficiency at late stages. As Smad4beta, but not Smad4alpha, is expressed at high levels maternally and during early gastrulation, our data suggest that although Smad4alpha and Smad4beta may have similar activities, they are differentially utilized during frog embryogenesis, with only Smad4beta being essential for mesoderm induction.

The effects of levetiracetam on neural tube development in the early stage of chick embryos.

PubMed

Guvenc, Yahya; Dalgic, Ali; Billur, Deniz; Karaoglu, Derya; Aydin, Sevim; Daglioglu, Ergun; Ozdol, Cagatay; Nacar, Osman Arikan; Yildirim, Ali Erdem; Belen, Deniz

2013-01-01

This study aimed to investigate the effects of a new generation antiepileptic agent, levetiracetam, on the neural tube development in a chick embryo model that corresponds to the first month of vertebral development in mammals. Forty-five Atabey® breed fertilized chicken eggs with no specific pathogens were randomly divided into 5 groups. All of the eggs were incubated at 37.8±2°C and 60±5 % relative humidity in an incubator. Group A was control group. The other eggs were applied physiological saline and drugs at a volume of 10 μL by the in ovo method at the 28th hour of the incubation period. Group B was given distilled water; Group C, physiological saline; Group D, Levetiracetam (L8668) at a dose equivalent to the treatment dose for humans (10 mg/ kg), and Group E, Levetiracetam (L8668) at a dose of 10 times the treatment dose. The embryos in all of the groups were removed from the shells at the 48th hour and morphologically and histologically evaluated. Of the 45 embryos incubated, neural tubes of 41 were closed and the embryos displayed normal development. Levetiracetam, at a dose equivalent to human treatment dose and 10 times the treatment dose, was shown not to cause neural tube defects in chick embryos.

Role of erythropoietin in the brain

PubMed Central

Noguchi, Constance Tom; Asavaritikrai, Pundit; Teng, Ruifeng; Jia, Yi

2007-01-01

Multi-tissue erythropoietin receptor (EPO-R) expression provides for erythropoietin (EPO) activity beyond its known regulation of red blood cell production. This review highlights the role of EPO and EPO-R in brain development and neuroprotection. EPO-R brain expression includes neural progenitor cells (NPC), neurons, glial cells and endothelial cells. EPO is produced in brain in a hypoxia sensitive manner, stimulates NPC proliferation and differentiation, and neuron survival, and contributes to ischemic preconditioning. Mice lacking EPO or EPO-R exhibit increased neural cell apoptosis during development before embryonic death due to severe anemia. EPO administration provides neural protection in animal models of brain ischemia and trauma, reducing the extent of injury and damage. EPO stimulation of endothelial cells contributes to neuroprotection and is of particular importance since only low levels of EPO appear to cross the blood-brain barrier when administered at high dose intravenously. The therapeutic potential of EPO for brain ischemia/trauma and neurodegenerative diseases has shown promise in early clinical trial and awaits further validation. PMID:17482474

A temperature-sensitive mutation in the nodal-related gene cyclops reveals that the floor plate is induced during gastrulation in zebrafish.

PubMed

Tian, Jing; Yam, Caleb; Balasundaram, Gayathri; Wang, Hui; Gore, Aniket; Sampath, Karuna

2003-07-01

The floor plate, a specialized group of cells in the ventral midline of the neural tube of vertebrates, plays crucial roles in patterning the central nervous system. Recent work from zebrafish, chick, chick-quail chimeras and mice to investigate the development of the floor plate have led to several models of floor-plate induction. One model suggests that the floor plate is formed by inductive signalling from the notochord to the overlying neural tube. The induction is thought to be mediated by notochord-derived Sonic hedgehog (Shh), a secreted protein, and requires direct cellular contact between the notochord and the neural tube. Another model proposes a role for the organizer in generating midline precursor cells that produce floor plate cells independent of notochord specification, and proposes that floor plate specification occurs early, during gastrulation. We describe a temperature-sensitive mutation that affects the zebrafish Nodal-related secreted signalling factor, Cyclops, and use it to address the issue of when the floor plate is induced in zebrafish. Zebrafish cyclops regulates the expression of shh in the ventral neural tube. Although null mutations in cyclops result in the lack of the medial floor plate, embryos homozygous for the temperature-sensitive mutation have floor plate cells at the permissive temperature and lack floor plate cells at the restrictive temperature. We use this mutant allele in temperature shift-up and shift-down experiments to answer a central question pertaining to the timing of vertebrate floor plate induction. Abrogation of Cyc/Nodal signalling in the temperature-sensitive mutant embryos at various stages indicates that the floor plate in zebrafish is induced early in development, during gastrulation. In addition, continuous Cyclops signalling is required through gastrulation for a complete ventral neural tube throughout the length of the neuraxis. Finally, by modulation of Nodal signalling levels in mutants and in ectopic overexpression experiments, we show that, similar to the requirements for prechordal plate mesendoderm fates, uninterrupted and high levels of Cyclops signalling are required for induction and specification of a complete ventral neural tube.

Neural Response to Reward as a Predictor of Rise in Depressive Symptoms in Adolescence

PubMed Central

Morgan, Judith K.; Olino, Thomas M.; McMakin, Dana L.; Ryan, Neal D.; Forbes, Erika E.

2012-01-01

Adolescence is a developmental period characterized by significant increases in the onset of depression, but also by increases in depressive symptoms, even among psychiatrically healthy youth. Disrupted reward function has been postulated as a critical factor in the development of depression, but it is still unclear which adolescents are particularly at risk for rising depressive symptoms. We provide a conceptual stance on gender, pubertal development, and reward type as potential moderators of the association between neural response to reward and rises in depressive symptoms. In addition, we describe preliminary findings that support claims of this conceptual stance. We propose that (1) status-related rewards may be particularly salient for eliciting neural response relevant to depressive symptoms in boys, whereas social rewards may be more salient for eliciting neural response relevant to depressive symptoms in girls and (2) the pattern of reduced striatal response and enhanced medial prefrontal response to reward may be particularly predictive of depressive symptoms in pubertal adolescents. We found that greater vmPFC activation when winning rewards predicted greater increases in depressive symptoms over two years, for boys only, and less striatal activation when anticipating rewards predicted greater increases in depressive symptoms over two years, for adolescents in mid to late pubertal stages but not those in pre to early puberty. We also propose directions for future studies, including the investigation of social vs. monetary reward directly and the longitudinal assessment of parallel changes in pubertal development, neural response to reward, and depressive symptoms. PMID:22521464

Neural networks for learning and prediction with applications to remote sensing and speech perception

NASA Astrophysics Data System (ADS)

Gjaja, Marin N.

1997-11-01

Neural networks for supervised and unsupervised learning are developed and applied to problems in remote sensing, continuous map learning, and speech perception. Adaptive Resonance Theory (ART) models are real-time neural networks for category learning, pattern recognition, and prediction. Unsupervised fuzzy ART networks synthesize fuzzy logic and neural networks, and supervised ARTMAP networks incorporate ART modules for prediction and classification. New ART and ARTMAP methods resulting from analyses of data structure, parameter specification, and category selection are developed. Architectural modifications providing flexibility for a variety of applications are also introduced and explored. A new methodology for automatic mapping from Landsat Thematic Mapper (TM) and terrain data, based on fuzzy ARTMAP, is developed. System capabilities are tested on a challenging remote sensing problem, prediction of vegetation classes in the Cleveland National Forest from spectral and terrain features. After training at the pixel level, performance is tested at the stand level, using sites not seen during training. Results are compared to those of maximum likelihood classifiers, back propagation neural networks, and K-nearest neighbor algorithms. Best performance is obtained using a hybrid system based on a convex combination of fuzzy ARTMAP and maximum likelihood predictions. This work forms the foundation for additional studies exploring fuzzy ARTMAP's capability to estimate class mixture composition for non-homogeneous sites. Exploratory simulations apply ARTMAP to the problem of learning continuous multidimensional mappings. A novel system architecture retains basic ARTMAP properties of incremental and fast learning in an on-line setting while adding components to solve this class of problems. The perceptual magnet effect is a language-specific phenomenon arising early in infant speech development that is characterized by a warping of speech sound perception. An unsupervised neural network model is proposed that embodies two principal hypotheses supported by experimental data--that sensory experience guides language-specific development of an auditory neural map and that a population vector can predict psychological phenomena based on map cell activities. Model simulations show how a nonuniform distribution of map cell firing preferences can develop from language-specific input and give rise to the magnet effect.

Dynamic changes in neural circuit topology following mild mechanical injury in vitro.

PubMed

Patel, Tapan P; Ventre, Scott C; Meaney, David F

2012-01-01

Despite its enormous incidence, mild traumatic brain injury is not well understood. One aspect that needs more definition is how the mechanical energy during injury affects neural circuit function. Recent developments in cellular imaging probes provide an opportunity to assess the dynamic state of neural networks with single-cell resolution. In this article, we developed imaging methods to assess the state of dissociated cortical networks exposed to mild injury. We estimated the imaging conditions needed to achieve accurate measures of network properties, and applied these methodologies to evaluate if mild mechanical injury to cortical neurons produces graded changes to either spontaneous network activity or altered network topology. We found that modest injury produced a transient increase in calcium activity that dissipated within 1 h after injury. Alternatively, moderate mechanical injury produced immediate disruption in network synchrony, loss in excitatory tone, and increased modular topology. A calcium-activated neutral protease (calpain) was a key intermediary in these changes; blocking calpain activation restored the network nearly completely to its pre-injury state. Together, these findings show a more complex change in neural circuit behavior than previously reported for mild mechanical injury, and highlight at least one important early mechanism responsible for these changes.

Neural differentiation promoted by truncated trkC receptors in collaboration with p75(NTR).

PubMed

Hapner, S J; Boeshore, K L; Large, T H; Lefcort, F

1998-09-01

trkC receptors, which serve critical functions during the development of the nervous system, are alternatively spliced to yield isoforms containing the catalytic tyrosine kinase domain (TK+) and truncated isoforms which lack this domain (TK-). To test for potential differences in their roles during early stages of neural development, TK+ and TK- isoforms were ectopically expressed in cultures of neural crest, the stem cell population that gives rise to the vast majority of the peripheral nervous system. NT-3 activation of ectopically expressed trkC TK+ receptors promoted both proliferation of neural crest cells and neuronal differentiation. Strikingly, the trkC TK- isoform was significantly more effective at promoting neuronal differentiation, but had no effect on proliferation. Furthermore, the trkC TK- response was dependent on a conserved receptor cytoplasmic domain and required the participation of the p75(NTR) neurotrophin receptor. Antibody-mediated receptor dimerization of TK+ receptors, but not TK- receptors, was sufficient to stimulate differentiation. These data identify a phenotypic response to activation of the trkC TK- receptor and demonstrate a functional interaction with p75(NTR), indicating there may be multiple trkC receptor-mediated systems guiding neuronal differentiation. Copyright 1998 Academic Press.

Concurrent OCT imaging of stimulus evoked retinal neural activation and hemodynamic responses

NASA Astrophysics Data System (ADS)

Son, Taeyoon; Wang, Benquan; Lu, Yiming; Chen, Yanjun; Cao, Dingcai; Yao, Xincheng

2017-02-01

It is well established that major retinal diseases involve distortions of the retinal neural physiology and blood vascular structures. However, the details of distortions in retinal neurovascular coupling associated with major eye diseases are not well understood. In this study, a multi-modal optical coherence tomography (OCT) imaging system was developed to enable concurrent imaging of retinal neural activity and vascular hemodynamics. Flicker light stimulation was applied to mouse retinas to evoke retinal neural responses and hemodynamic changes. The OCT images were acquired continuously during the pre-stimulation, light-stimulation, and post-stimulation phases. Stimulus-evoked intrinsic optical signals (IOSs) and hemodynamic changes were observed over time in blood-free and blood regions, respectively. Rapid IOSs change occurred almost immediately after stimulation. Both positive and negative signals were observed in adjacent retinal areas. The hemodynamic changes showed time delays after stimulation. The signal magnitudes induced by light stimulation were observed in blood regions and did not show significant changes in blood-free regions. These differences may arise from different mechanisms in blood vessels and neural tissues in response to light stimulation. These characteristics agreed well with our previous observations in mouse retinas. Further development of the multimodal OCT may provide a new imaging method for studying how retinal structures and metabolic and neural functions are affected by age-related macular degeneration (AMD), glaucoma, diabetic retinopathy (DR), and other diseases, which promises novel noninvasive biomarkers for early disease detection and reliable treatment evaluations of eye diseases.

Perineuronal net, CSPG receptor and their regulation of neural plasticity.

PubMed

Miao, Qing-Long; Ye, Qian; Zhang, Xiao-Hui

2014-08-25

Perineuronal nets (PNNs) are reticular structures resulting from the aggregation of extracellular matrix (ECM) molecules around the cell body and proximal neurite of specific population of neurons in the central nervous system (CNS). Since the first description of PNNs by Camillo Golgi in 1883, the molecular composition, developmental formation and potential functions of these specialized extracellular matrix structures have only been intensively studied over the last few decades. The main components of PNNs are hyaluronan (HA), chondroitin sulfate proteoglycans (CSPGs) of the lectican family, link proteins and tenascin-R. PNNs appear late in neural development, inversely correlating with the level of neural plasticity. PNNs have long been hypothesized to play a role in stabilizing the extracellular milieu, which secures the characteristic features of enveloped neurons and protects them from the influence of malicious agents. Aberrant PNN signaling can lead to CNS dysfunctions like epilepsy, stroke and Alzheimer's disease. On the other hand, PNNs create a barrier which constrains the neural plasticity and counteracts the regeneration after nerve injury. Digestion of PNNs with chondroitinase ABC accelerates functional recovery from the spinal cord injury and restores activity-dependent mechanisms for modifying neuronal connections in the adult animals, indicating that PNN is an important regulator of neural plasticity. Here, we review recent progress in the studies on the formation of PNNs during early development and the identification of CSPG receptor - an essential molecular component of PNN signaling, along with a discussion on their unique regulatory roles in neural plasticity.

Early neural activation during facial affect processing in adolescents with Autism Spectrum Disorder.

PubMed

Leung, Rachel C; Pang, Elizabeth W; Cassel, Daniel; Brian, Jessica A; Smith, Mary Lou; Taylor, Margot J

2015-01-01

Impaired social interaction is one of the hallmarks of Autism Spectrum Disorder (ASD). Emotional faces are arguably the most critical visual social stimuli and the ability to perceive, recognize, and interpret emotions is central to social interaction and communication, and subsequently healthy social development. However, our understanding of the neural and cognitive mechanisms underlying emotional face processing in adolescents with ASD is limited. We recruited 48 adolescents, 24 with high functioning ASD and 24 typically developing controls. Participants completed an implicit emotional face processing task in the MEG. We examined spatiotemporal differences in neural activation between the groups during implicit angry and happy face processing. While there were no differences in response latencies between groups across emotions, adolescents with ASD had lower accuracy on the implicit emotional face processing task when the trials included angry faces. MEG data showed atypical neural activity in adolescents with ASD during angry and happy face processing, which included atypical activity in the insula, anterior and posterior cingulate and temporal and orbitofrontal regions. Our findings demonstrate differences in neural activity during happy and angry face processing between adolescents with and without ASD. These differences in activation in social cognitive regions may index the difficulties in face processing and in comprehension of social reward and punishment in the ASD group. Thus, our results suggest that atypical neural activation contributes to impaired affect processing, and thus social cognition, in adolescents with ASD.

Ca(2+) coding and decoding strategies for the specification of neural and renal precursor cells during development.

PubMed

Moreau, Marc; Néant, Isabelle; Webb, Sarah E; Miller, Andrew L; Riou, Jean-François; Leclerc, Catherine

2016-03-01

During embryogenesis, a rise in intracellular Ca(2+) is known to be a widespread trigger for directing stem cells towards a specific tissue fate, but the precise Ca(2+) signalling mechanisms involved in achieving these pleiotropic effects are still poorly understood. In this review, we compare the Ca(2+) signalling events that appear to be one of the first steps in initiating and regulating both neural determination (neural induction) and kidney development (nephrogenesis). We have highlighted the necessary and sufficient role played by Ca(2+) influx and by Ca(2+) transients in the determination and differentiation of pools of neural or renal precursors. We have identified new Ca(2+) target genes involved in neural induction and we showed that the same Ca(2+) early target genes studied are not restricted to neural tissue but are also present in other tissues, principally in the pronephros. In this review, we also described a mechanism whereby the transcriptional control of gene expression during neurogenesis and nephrogenesis might be directly controlled by Ca(2+) signalling. This mechanism involves members of the Kcnip family such that a change in their binding properties to specific DNA sites is a result of Ca(2+) binding to EF-hand motifs. The different functions of Ca(2+) signalling during these two events illustrate the versatility of Ca(2+) as a second messenger. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cannabis Use and Memory Brain Function in Adolescent Boys: A Cross-Sectional Multicenter Functional Magnetic Resonance Imaging Study

ERIC Educational Resources Information Center

Jager, Gerry; Block, Robert I.; Luijten, Maartje; Ramsey, Nick F.

2010-01-01

Objective: Early-onset cannabis use has been associated with later use/abuse, mental health problems (psychosis, depression), and abnormal development of cognition and brain function. During adolescence, ongoing neurodevelopmental maturation and experience shape the neural circuitry underlying complex cognitive functions such as memory and…

Continuity and Change in Children's Longitudinal Neural Responses to Numbers

ERIC Educational Resources Information Center

Emerson, Robert W.; Cantlon, Jessica F.

2015-01-01

Human children possess the ability to approximate numerical quantity nonverbally from a young age. Over the course of early childhood, children develop increasingly precise representations of numerical values, including a symbolic number system that allows them to conceive of numerical information as Arabic numerals or number words. Functional…

Early alcohol exposure impairs ocular dominance plasticity throughout the critical period.

PubMed

Medina, Alexandre E; Ramoa, Ary S

2005-06-09

Animal models of fetal alcohol syndrome (FAS) have revealed an impairment of sensory neocortex plasticity. Here, we examine whether early alcohol exposure leads to a permanent impairment of ocular dominance plasticity (OD) or to an alteration in the timing of the critical period. Ferrets were exposed to alcohol during a brief period of development prior to eye opening and effects of monocular deprivation examined during early, mid and late critical period. Single-unit electrophysiology revealed markedly reduced OD plasticity at every age examined. This finding provides evidence that early alcohol exposure does not affect the timing or duration of the critical period of OD plasticity and suggests an enduring impairment of neural plasticity in FAS.

Resilience in mathematics after early brain injury: The roles of parental input and early plasticity.

PubMed

Glenn, Dana E; Demir-Lira, Özlem Ece; Gibson, Dominic J; Congdon, Eliza L; Levine, Susan C

2018-04-01

Children with early focal unilateral brain injury show remarkable plasticity in language development. However, little is known about how early brain injury influences mathematical learning. Here, we examine early number understanding, comparing cardinal number knowledge of typically developing children (TD) and children with pre- and perinatal lesions (BI) between 42 and 50 months of age. We also examine how this knowledge relates to the number words children hear from their primary caregivers early in life. We find that children with BI, are, on average, slightly behind TD children in both cardinal number knowledge and later mathematical performance, and show slightly slower learning rates than TD children in cardinal number knowledge during the preschool years. We also find that parents' "number talk" to their toddlers predicts later mathematical ability for both TD children and children with BI. These findings suggest a relatively optimistic story in which neural plasticity is at play in children's mathematical development following early brain injury. Further, the effects of early number input suggest that intervening to enrich the number talk that children with BI hear during the preschool years could narrow the math achievement gap. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Contributions of Dynamic Systems Theory to Cognitive Development

PubMed Central

Spencer, John P.; Austin, Andrew; Schutte, Anne R.

2015-01-01

This paper examines the contributions of dynamic systems theory to the field of cognitive development, focusing on modeling using dynamic neural fields. A brief overview highlights the contributions of dynamic systems theory and the central concepts of dynamic field theory (DFT). We then probe empirical predictions and findings generated by DFT around two examples—the DFT of infant perseverative reaching that explains the Piagetian A-not-B error, and the DFT of spatial memory that explain changes in spatial cognition in early development. A systematic review of the literature around these examples reveals that computational modeling is having an impact on empirical research in cognitive development; however, this impact does not extend to neural and clinical research. Moreover, there is a tendency for researchers to interpret models narrowly, anchoring them to specific tasks. We conclude on an optimistic note, encouraging both theoreticians and experimentalists to work toward a more theory-driven future. PMID:26052181

Attachment in integrative neuroscientific perspective.

PubMed

Hruby, Radovan; Hasto, Jozef; Minarik, Peter

2011-01-01

Attachment theory is a very influential general concept of human social and emotional development, which emphasizes the role of early mother-infant interactions for infant's adaptive behavioural and stress copying strategies, personality organization and mental health. Individuals with disrupted development of secure attachment to mother/primary caregiver are at higher risk of developing mental disorders. This theory consists of the complex developmental psycho-neurobiological model of attachment and emerges from principles of psychoanalysis, evolutionary biology, cognitive-developmental psychology, ethology, physiology and control systems theory. The progress of modern neuroscience enables interpretation of neurobiological aspects of the theory as multi-level neural interactions and functional development of important neural structures, effects of neuromediattors, hormones and essential neurobiological processes including emotional, cognitive, social interactions and the special key role of mentalizing. It has multiple neurobiological, neuroendocrine, neurophysiological, ethological, genetic, developmental, psychological, psychotherapeutic and neuropsychiatric consequences and is a prototype of complex neuroscientific concept as interpretation of modern integrated neuroscience.

The development and modeling of devices and paradigms for transcranial magnetic stimulation

PubMed Central

Goetz, Stefan M.; Deng, Zhi-De

2017-01-01

Magnetic stimulation is a noninvasive neurostimulation technique that can evoke action potentials and modulate neural circuits through induced electric fields. Biophysical models of magnetic stimulation have become a major driver for technological developments and the understanding of the mechanisms of magnetic neurostimulation and neuromodulation. Major technological developments involve stimulation coils with different spatial characteristics and pulse sources to control the pulse waveform. While early technological developments were the result of manual design and invention processes, there is a trend in both stimulation coil and pulse source design to mathematically optimize parameters with the help of computational models. To date, macroscopically highly realistic spatial models of the brain as well as peripheral targets, and user-friendly software packages enable researchers and practitioners to simulate the treatment-specific and induced electric field distribution in the brains of individual subjects and patients. Neuron models further introduce the microscopic level of neural activation to understand the influence of activation dynamics in response to different pulse shapes. A number of models that were designed for online calibration to extract otherwise covert information and biomarkers from the neural system recently form a third branch of modeling. PMID:28443696

The development and modelling of devices and paradigms for transcranial magnetic stimulation.

PubMed

Goetz, Stefan M; Deng, Zhi-De

2017-04-01

Magnetic stimulation is a non-invasive neurostimulation technique that can evoke action potentials and modulate neural circuits through induced electric fields. Biophysical models of magnetic stimulation have become a major driver for technological developments and the understanding of the mechanisms of magnetic neurostimulation and neuromodulation. Major technological developments involve stimulation coils with different spatial characteristics and pulse sources to control the pulse waveform. While early technological developments were the result of manual design and invention processes, there is a trend in both stimulation coil and pulse source design to mathematically optimize parameters with the help of computational models. To date, macroscopically highly realistic spatial models of the brain, as well as peripheral targets, and user-friendly software packages enable researchers and practitioners to simulate the treatment-specific and induced electric field distribution in the brains of individual subjects and patients. Neuron models further introduce the microscopic level of neural activation to understand the influence of activation dynamics in response to different pulse shapes. A number of models that were designed for online calibration to extract otherwise covert information and biomarkers from the neural system recently form a third branch of modelling.

Chondroitin sulfate effects on neural stem cell differentiation.

PubMed

Canning, David R; Brelsford, Natalie R; Lovett, Neil W

2016-01-01

We have investigated the role chondroitin sulfate has on cell interactions during neural plate formation in the early chick embryo. Using tissue culture isolates from the prospective neural plate, we have measured neural gene expression profiles associated with neural stem cell differentiation. Removal of chondroitin sulfate from stage 4 neural plate tissue leads to altered associations of N-cadherin-positive neural progenitors and causes changes in the normal sequence of neural marker gene expression. Absence of chondroitin sulfate in the neural plate leads to reduced Sox2 expression and is accompanied by an increase in the expression of anterior markers of neural regionalization. Results obtained in this study suggest that the presence of chondroitin sulfate in the anterior chick embryo is instrumental in maintaining cells in the neural precursor state.

Neural tube and other developmental anomalies in the guinea pig following maternal hyperthermia during early neural tube development.

PubMed

Cawdell-Smith, J; Upfold, J; Edwards, M; Smith, M

1992-01-01

Guinea pigs were exposed to hyperthermia for 1 hr once or twice on day 11, 12, 13, or 14 (E11-E14) of pregnancy. The mean rectal temperatures were elevated by 3.4 degrees C-4.0 degrees C. This treatment resulted in a marked elevation of rates of resorption and developmental defects in embryos examined at day E23. The defects observed were those affecting the neural tube (NTD) (exencephaly, encephaloceles, and microphthalmia), kyphosis/scoliosis, branchial arch defects, and pericardial edema. Embryos with NTD and kyphosis/scoliosis have not been found among newborn guinea pigs to date following maternal heat exposure on days E12-E14. It appears that embryos with these defects are filtered out by resorption or abortion by days E30-E35.

Mouse IDGenes: a reference database for genetic interactions in the developing mouse brain

PubMed Central

Matthes, Michaela; Preusse, Martin; Zhang, Jingzhong; Schechter, Julia; Mayer, Daniela; Lentes, Bernd; Theis, Fabian; Prakash, Nilima; Wurst, Wolfgang; Trümbach, Dietrich

2014-01-01

The study of developmental processes in the mouse and other vertebrates includes the understanding of patterning along the anterior–posterior, dorsal–ventral and medial– lateral axis. Specifically, neural development is also of great clinical relevance because several human neuropsychiatric disorders such as schizophrenia, autism disorders or drug addiction and also brain malformations are thought to have neurodevelopmental origins, i.e. pathogenesis initiates during childhood and adolescence. Impacts during early neurodevelopment might also predispose to late-onset neurodegenerative disorders, such as Parkinson’s disease. The neural tube develops from its precursor tissue, the neural plate, in a patterning process that is determined by compartmentalization into morphogenetic units, the action of local signaling centers and a well-defined and locally restricted expression of genes and their interactions. While public databases provide gene expression data with spatio-temporal resolution, they usually neglect the genetic interactions that govern neural development. Here, we introduce Mouse IDGenes, a reference database for genetic interactions in the developing mouse brain. The database is highly curated and offers detailed information about gene expressions and the genetic interactions at the developing mid-/hindbrain boundary. To showcase the predictive power of interaction data, we infer new Wnt/β-catenin target genes by machine learning and validate one of them experimentally. The database is updated regularly. Moreover, it can easily be extended by the research community. Mouse IDGenes will contribute as an important resource to the research on mouse brain development, not exclusively by offering data retrieval, but also by allowing data input. Database URL: http://mouseidgenes.helmholtz-muenchen.de. PMID:25145340

Mouse IDGenes: a reference database for genetic interactions in the developing mouse brain.

PubMed

Matthes, Michaela; Preusse, Martin; Zhang, Jingzhong; Schechter, Julia; Mayer, Daniela; Lentes, Bernd; Theis, Fabian; Prakash, Nilima; Wurst, Wolfgang; Trümbach, Dietrich

2014-01-01

The study of developmental processes in the mouse and other vertebrates includes the understanding of patterning along the anterior-posterior, dorsal-ventral and medial- lateral axis. Specifically, neural development is also of great clinical relevance because several human neuropsychiatric disorders such as schizophrenia, autism disorders or drug addiction and also brain malformations are thought to have neurodevelopmental origins, i.e. pathogenesis initiates during childhood and adolescence. Impacts during early neurodevelopment might also predispose to late-onset neurodegenerative disorders, such as Parkinson's disease. The neural tube develops from its precursor tissue, the neural plate, in a patterning process that is determined by compartmentalization into morphogenetic units, the action of local signaling centers and a well-defined and locally restricted expression of genes and their interactions. While public databases provide gene expression data with spatio-temporal resolution, they usually neglect the genetic interactions that govern neural development. Here, we introduce Mouse IDGenes, a reference database for genetic interactions in the developing mouse brain. The database is highly curated and offers detailed information about gene expressions and the genetic interactions at the developing mid-/hindbrain boundary. To showcase the predictive power of interaction data, we infer new Wnt/β-catenin target genes by machine learning and validate one of them experimentally. The database is updated regularly. Moreover, it can easily be extended by the research community. Mouse IDGenes will contribute as an important resource to the research on mouse brain development, not exclusively by offering data retrieval, but also by allowing data input. http://mouseidgenes.helmholtz-muenchen.de. © The Author(s) 2014. Published by Oxford University Press.

Neural crest contribution to lingual mesenchyme, epithelium and developing taste papillae and taste buds

PubMed Central

Liu, Hong-Xiang; Komatsu, Yoshihiro; Mishina, Yuji; Mistretta, Charlotte M.

2012-01-01

The epithelium of mammalian tongue hosts most of the taste buds that transduce gustatory stimuli into neural signals. In the field of taste biology, taste bud cells have been described as arising from “local epithelium”, in distinction from many other receptor organs that are derived from neurogenic ectoderm including neural crest (NC). In fact, contribution of NC to both epithelium and mesenchyme in the developing tongue is not fully understood. In the present study we used two independent, well-characterized mouse lines, Wnt1-Cre and P0-Cre that express Cre recombinase in a NC-specific manner, in combination with two Cre reporter mouse lines, R26R and ZEG, and demonstrate a contribution of NC-derived cells to both tongue mesenchyme and epithelium including taste papillae and taste buds. In tongue mesenchyme, distribution of NC-derived cells is in close association with taste papillae. In tongue epithelium, labeled cells are observed in an initial scattered distribution and progress to a clustered pattern between papillae, and within papillae and early taste buds. This provides evidence for a contribution of NC to lingual epithelium. Together with previous reports for the origin of taste bud cells from local epithelium in postnatal mouse, we propose that NC cells migrate into and reside in the epithelium of the tongue primordium at an early embryonic stage, acquire epithelial cell phenotypes, and undergo cell proliferation and differentiation that is involved in the development of taste papillae and taste buds. Our findings lead to a new concept about derivation of taste bud cells that include a NC origin. PMID:22659543

Roles of ADAM13-regulated Wnt activity in early Xenopus eye development

PubMed Central

Wei, Shuo; Xu, Guofeng; Bridges, Lance C.; Williams, Phoebe; Nakayama, Takuya; Shah, Anoop; Grainger, Robert M.; White, Judith M.; DeSimone, Douglas W.

2012-01-01

Pericellular proteolysis by ADAM family metalloproteinases has been widely implicated in cell signaling and development. We recently found that Xenopus ADAM13, an ADAM metalloproteinase, is required for activation of canonical Wnt signaling during cranial neural crest (CNC) induction by regulating a novel crosstalk between Wnt and ephrin B (EfnB) signaling pathways (Wei et al., 2010b). In the present study we show that the metalloproteinase activity of ADAM13 also plays important roles in eye development in X. tropicalis. Knockdown of ADAM13 results in reduced expression of eye field markers pax6 and rx1, as well as that of the pan-neural marker sox2. Activation of canonical Wnt signaling or inhibition of forward EfnB signaling rescues the eye defects caused by loss of ADAM13, suggesting that ADAM13 functions through regulation of the EfnB-Wnt pathway interaction. Downstream of Wnt, the head inducer Cerberus was identified as an effector that mediates ADAM13 function in early eye field formation. Furthermore, ectopic expression of the Wnt target gene snail2 restores cerberus expression and rescues the eye defects caused by ADAM13 knockdown. Together these data suggest an important role of ADAM13-regulated Wnt activity in eye development in Xenopus. PMID:22227340

Mirroring and beyond: coupled dynamics as a generalized framework for modelling social interactions

PubMed Central

Hasson, Uri; Frith, Chris D.

2016-01-01

When people observe one another, behavioural alignment can be detected at many levels, from the physical to the mental. Likewise, when people process the same highly complex stimulus sequences, such as films and stories, alignment is detected in the elicited brain activity. In early sensory areas, shared neural patterns are coupled to the low-level properties of the stimulus (shape, motion, volume, etc.), while in high-order brain areas, shared neural patterns are coupled to high-levels aspects of the stimulus, such as meaning. Successful social interactions require such alignments (both behavioural and neural), as communication cannot occur without shared understanding. However, we need to go beyond simple, symmetric (mirror) alignment once we start interacting. Interactions are dynamic processes, which involve continuous mutual adaptation, development of complementary behaviour and division of labour such as leader–follower roles. Here, we argue that interacting individuals are dynamically coupled rather than simply aligned. This broader framework for understanding interactions can encompass both processes by which behaviour and brain activity mirror each other (neural alignment), and situations in which behaviour and brain activity in one participant are coupled (but not mirrored) to the dynamics in the other participant. To apply these more sophisticated accounts of social interactions to the study of the underlying neural processes we need to develop new experimental paradigms and novel methods of data analysis PMID:27069044

The Evolution and Development of Neural Superposition

PubMed Central

Agi, Egemen; Langen, Marion; Altschuler, Steven J.; Wu, Lani F.; Zimmermann, Timo

2014-01-01

Visual systems have a rich history as model systems for the discovery and understanding of basic principles underlying neuronal connectivity. The compound eyes of insects consist of up to thousands of small unit eyes that are connected by photoreceptor axons to set up a visual map in the brain. The photoreceptor axon terminals thereby represent neighboring points seen in the environment in neighboring synaptic units in the brain. Neural superposition is a special case of such a wiring principle, where photoreceptors from different unit eyes that receive the same input converge upon the same synaptic units in the brain. This wiring principle is remarkable, because each photoreceptor in a single unit eye receives different input and each individual axon, among thousands others in the brain, must be sorted together with those few axons that have the same input. Key aspects of neural superposition have been described as early as 1907. Since then neuroscientists, evolutionary and developmental biologists have been fascinated by how such a complicated wiring principle could evolve, how it is genetically encoded, and how it is developmentally realized. In this review article, we will discuss current ideas about the evolutionary origin and developmental program of neural superposition. Our goal is to identify in what way the special case of neural superposition can help us answer more general questions about the evolution and development of genetically “hard-wired” synaptic connectivity in the brain. PMID:24912630

A molecular atlas of the developing ectoderm defines neural, neural crest, placode, and nonneural progenitor identity in vertebrates.

PubMed

Plouhinec, Jean-Louis; Medina-Ruiz, Sofía; Borday, Caroline; Bernard, Elsa; Vert, Jean-Philippe; Eisen, Michael B; Harland, Richard M; Monsoro-Burq, Anne H

2017-10-01

During vertebrate neurulation, the embryonic ectoderm is patterned into lineage progenitors for neural plate, neural crest, placodes and epidermis. Here, we use Xenopus laevis embryos to analyze the spatial and temporal transcriptome of distinct ectodermal domains in the course of neurulation, during the establishment of cell lineages. In order to define the transcriptome of small groups of cells from a single germ layer and to retain spatial information, dorsal and ventral ectoderm was subdivided along the anterior-posterior and medial-lateral axes by microdissections. Principal component analysis on the transcriptomes of these ectoderm fragments primarily identifies embryonic axes and temporal dynamics. This provides a genetic code to define positional information of any ectoderm sample along the anterior-posterior and dorsal-ventral axes directly from its transcriptome. In parallel, we use nonnegative matrix factorization to predict enhanced gene expression maps onto early and mid-neurula embryos, and specific signatures for each ectoderm area. The clustering of spatial and temporal datasets allowed detection of multiple biologically relevant groups (e.g., Wnt signaling, neural crest development, sensory placode specification, ciliogenesis, germ layer specification). We provide an interactive network interface, EctoMap, for exploring synexpression relationships among genes expressed in the neurula, and suggest several strategies to use this comprehensive dataset to address questions in developmental biology as well as stem cell or cancer research.

The evolution and development of neural superposition.

PubMed

Agi, Egemen; Langen, Marion; Altschuler, Steven J; Wu, Lani F; Zimmermann, Timo; Hiesinger, Peter Robin

2014-01-01

Visual systems have a rich history as model systems for the discovery and understanding of basic principles underlying neuronal connectivity. The compound eyes of insects consist of up to thousands of small unit eyes that are connected by photoreceptor axons to set up a visual map in the brain. The photoreceptor axon terminals thereby represent neighboring points seen in the environment in neighboring synaptic units in the brain. Neural superposition is a special case of such a wiring principle, where photoreceptors from different unit eyes that receive the same input converge upon the same synaptic units in the brain. This wiring principle is remarkable, because each photoreceptor in a single unit eye receives different input and each individual axon, among thousands others in the brain, must be sorted together with those few axons that have the same input. Key aspects of neural superposition have been described as early as 1907. Since then neuroscientists, evolutionary and developmental biologists have been fascinated by how such a complicated wiring principle could evolve, how it is genetically encoded, and how it is developmentally realized. In this review article, we will discuss current ideas about the evolutionary origin and developmental program of neural superposition. Our goal is to identify in what way the special case of neural superposition can help us answer more general questions about the evolution and development of genetically "hard-wired" synaptic connectivity in the brain.

A molecular atlas of the developing ectoderm defines neural, neural crest, placode, and nonneural progenitor identity in vertebrates

PubMed Central

Borday, Caroline; Bernard, Elsa; Vert, Jean-Philippe; Eisen, Michael B.; Harland, Richard M.

2017-01-01

During vertebrate neurulation, the embryonic ectoderm is patterned into lineage progenitors for neural plate, neural crest, placodes and epidermis. Here, we use Xenopus laevis embryos to analyze the spatial and temporal transcriptome of distinct ectodermal domains in the course of neurulation, during the establishment of cell lineages. In order to define the transcriptome of small groups of cells from a single germ layer and to retain spatial information, dorsal and ventral ectoderm was subdivided along the anterior-posterior and medial-lateral axes by microdissections. Principal component analysis on the transcriptomes of these ectoderm fragments primarily identifies embryonic axes and temporal dynamics. This provides a genetic code to define positional information of any ectoderm sample along the anterior-posterior and dorsal-ventral axes directly from its transcriptome. In parallel, we use nonnegative matrix factorization to predict enhanced gene expression maps onto early and mid-neurula embryos, and specific signatures for each ectoderm area. The clustering of spatial and temporal datasets allowed detection of multiple biologically relevant groups (e.g., Wnt signaling, neural crest development, sensory placode specification, ciliogenesis, germ layer specification). We provide an interactive network interface, EctoMap, for exploring synexpression relationships among genes expressed in the neurula, and suggest several strategies to use this comprehensive dataset to address questions in developmental biology as well as stem cell or cancer research. PMID:29049289

Two Pore Channel 2 Differentially Modulates Neural Differentiation of Mouse Embryonic Stem Cells

PubMed Central

Zhang, Zhe-Hao; Lu, Ying-Ying; Yue, Jianbo

2013-01-01

Nicotinic acid adenine dinucleotide phosphate (NAADP) is an endogenous Ca2+ mobilizing nucleotide presented in various species. NAADP mobilizes Ca2+ from acidic organelles through two pore channel 2 (TPC2) in many cell types and it has been previously shown that NAADP can potently induce neuronal differentiation in PC12 cells. Here we examined the role of TPC2 signaling in the neural differentiation of mouse embryonic stem (ES) cells. We found that the expression of TPC2 was markedly decreased during the initial ES cell entry into neural progenitors, and the levels of TPC2 gradually rebounded during the late stages of neurogenesis. Correspondingly, TPC2 knockdown accelerated mouse ES cell differentiation into neural progenitors but inhibited these neural progenitors from committing to neurons. Overexpression of TPC2, on the other hand, inhibited mouse ES cell from entering the early neural lineage. Interestingly, TPC2 knockdown had no effect on the differentiation of astrocytes and oligodendrocytes of mouse ES cells. Taken together, our data indicate that TPC2 signaling plays a temporal and differential role in modulating the neural lineage entry of mouse ES cells, in that TPC2 signaling inhibits ES cell entry to early neural progenitors, but is required for late neuronal differentiation. PMID:23776607

Evolutionary Origins for Social Vocalization in a Vertebrate Hindbrain–Spinal Compartment

PubMed Central

Bass, Andrew H.; Gilland, Edwin H.; Baker, Robert

2008-01-01

The macroevolutionary events leading to neural innovations for social communication, such as vocalization, are essentially unexplored. Many fish vocalize during female courtship and territorial defense, as do amphibians, birds, and mammals. Here, we map the neural circuitry for vocalization in larval fish and show that the vocal network develops in a segment-like region across the most caudal hindbrain and rostral spinal cord. Taxonomic analysis demonstrates a highly conserved pattern between fish and all major lineages of vocal tetrapods. We propose that the vocal basis for acoustic communication among vertebrates evolved from an ancestrally shared developmental compartment already present in the early fishes. PMID:18635807

Mapping of Courtship Behavior-Induced Neural Activity in the Thoracic Ganglia of Silkmoth Bombyx mori by an Immediate Early Gene, Hr38.

PubMed

Morishita, Koudai; Iwami, Masafumi; Kiya, Taketoshi

2018-06-01

In the central nervous system of insects, motor patterns are generated in the thoracic ganglia under the control of brain, where sensory information is integrated and behavioral decisions are made. Previously, we established neural activity-mapping methods using an immediate early gene, BmHr38, as a neural activity marker in the brain of male silkmoth Bombyx mori. In the present study, to gain insights into neural mechanisms of motor-pattern generation in the thoracic ganglia, we investigated expression of BmHr38 in response to sex pheromone-induced courtship behavior. Levels of BmHr38 expression were strongly correlated between the brain and thoracic ganglia, suggesting that neural activity in the thoracic ganglia is tightly controlled by the brain. In situ hybridization of BmHr38 revealed that 20-30% of thoracic neurons are activated by courtship behavior. Using serial sections, we constructed a comprehensive map of courtship behaviorinduced activity in the thoracic ganglia. These results provide important clues into how complex courtship behavior is generated in the neural circuits of thoracic ganglia.

Neural processing of race by individuals with Williams syndrome: Do they show the other-race effect? (And why it matters)

PubMed Central

Fishman, Inna; Ng, Rowena; Bellugi, Ursula

2012-01-01

Williams syndrome (WS) is a genetic condition with a distinctive social phenotype characterized by excessive sociability, accompanied by a relative proficiency in face recognition, despite severe deficits in visuospatial domain of cognition. This consistent phenotypic characteristic and the relative homogeneity of the WS genotype make WS a compelling human model for examining the genotype-phenotype relations, especially with respect to social behavior. Following up on a recent report suggesting that individuals with WS do not show race bias and racial stereotyping, this study was designed to investigate the neural correlates of the perception of faces from different races, in individuals with WS as compared to typically developing (TD) controls. Caucasian WS and TD participants performed a gender identification task with own-race (White) and other-race (Black) faces while event-related potentials (ERPs) were recorded. In line with previous studies with TD participants, other-race faces elicited larger amplitudes ERPs within the first 200 ms following the face onset, in WS and TD participants alike. These results suggest that, just like their TD counterparts, individuals with WS differentially processed faces of own- vs. other-race, at relatively early stages of processing, starting as early as 115 ms after the face onset. Overall, these results indicate that neural processing of faces in individuals with WS is moderated by race at early perceptual stages, calling for a reconsideration of the previous claim that they are uniquely insensitive to race. PMID:22022973

ADAM13 Induces Cranial Neural Crest by Cleaving Class B Ephrins and Regulating Wnt Signaling

PubMed Central

Wei, Shuo; Xu, Guofeng; Bridges, Lance C.; Williams, Phoebe; White, Judith M.; DeSimone, Douglas W.

2010-01-01

SUMMARY The cranial neural crest (CNC) are multipotent embryonic cells that contribute to craniofacial structures and other cells and tissues of the vertebrate head. During embryogenesis, CNC is induced at the neural plate boundary through the interplay of several major signaling pathways. Here we report that the metalloproteinase activity of ADAM13 is required for early induction of CNC in Xenopus. In both cultured cells and X. tropicalis embryos, membrane-bound Ephrins (Efns) B1 and B2 were identified as substrates for ADAM13. ADAM13 upregulates canonical Wnt signaling and early expression of the transcription factor snail2, whereas EfnB1 inhibits the canonical Wnt pathway and snail2 expression. We propose that by cleaving class B Efns, ADAM13 promotes canonical Wnt signaling and early CNC induction. PMID:20708595

Early exposure of rotating magnetic fields promotes central nervous regeneration in planarian Girardia sinensis.

PubMed

Chen, Qiang; Lin, Gui-miao; Wu, Nan; Tang, Sheng-wei; Zheng, Zhi-jia; Lin, Marie Chia-mi; Xu, Gai-xia; Liu, Hao; Deng, Yue-yue; Zhang, Xiao-yun; Chen, Si-ping; Wang, Xiao-mei; Niu, Han-ben

2016-05-01

Magnetic field exposure is an accepted safe and effective modality for nerve injury. However, it is clinically used only as a supplement or salvage therapy at the later stage of treatment. Here, we used a planarian Girardia sinensis decapitated model to investigate beneficial effects of early rotary non-uniform magnetic fields (RMFs) exposure on central nervous regeneration. Our results clearly indicated that magnetic stimulation induced from early RMFs exposure significantly promoted neural regeneration of planarians. This stimulating effect is frequency and intensity dependent. Optimum effects were obtained when decapitated planarians were cultured at 20 °C, starved for 3 days before head-cutting, and treated with 6 Hz 0.02 T RMFs. At early regeneration stage, RMFs exposure eliminated edema around the wound and facilitated subsequent formation of blastema. It also accelerated cell proliferation and recovery of neuron functionality. Early RMFs exposure up-regulated expression of neural regeneration related proteins, EGR4 and Netrin 2, and mature nerve cell marker proteins, NSE and NPY. These results suggest that RMFs therapy produced early and significant benefit in central nervous regeneration, and should be clinically used at the early stage of neural regeneration, with appropriate optimal frequency and intensity. © 2016 Wiley Periodicals, Inc.

Motor development and motor resonance difficulties in autism: relevance to early intervention for language and communication skills

PubMed Central

McCleery, Joseph P.; Elliott, Natasha A.; Sampanis, Dimitrios S.; Stefanidou, Chrysi A.

2013-01-01

Research suggests that a sub-set of children with autism experience notable difficulties and delays in motor skills development, and that a large percentage of children with autism experience deficits in motor resonance. These motor-related deficiencies, which evidence suggests are present from a very early age, are likely to negatively affect social-communicative and language development in this population. Here, we review evidence for delayed, impaired, and atypical motor development in infants and children with autism. We then carefully review and examine the current language and communication-based intervention research that is relevant to motor and motor resonance (i.e., neural “mirroring” mechanisms activated when we observe the actions of others) deficits in children with autism. Finally, we describe research needs and future directions and developments for early interventions aimed at addressing the speech/language and social-communication development difficulties in autism from a motor-related perspective. PMID:23630476

The development of the neural crest in the human

PubMed Central

O’Rahilly, Ronan; Müller, Fabiola

2007-01-01

The first systematic account of the neural crest in the human has been prepared after an investigation of 185 serially sectioned staged embryos, aided by graphic reconstructions. As many as fourteen named topographical subdivisions of the crest were identified and eight of them give origin to ganglia (Table 2). Significant findings in the human include the following. (1) An indication of mesencephalic neural crest is discernible already at stage 9, and trigeminal, facial, and postotic components can be detected at stage 10. (2) Crest was not observed at the level of diencephalon 2. Although pre-otic crest from the neural folds is at first continuous (stage 10), crest-free zones are soon observable (stage 11) in Rh.1, 3, and 5. (3) Emigration of cranial neural crest from the neural folds at the neurosomatic junction begins before closure of the rostral neuropore, and later crest cells do not accumulate above the neural tube. (4) The trigeminal, facial, glossopharyngeal and vagal ganglia, which develop from crest that emigrates before the neural folds have fused, continue to receive contributions from the roof plate of the neural tube after fusion of the folds. (5) The nasal crest and the terminalis-vomeronasal complex are the last components of the cranial crest to appear (at stage 13) and they persist longer. (6) The optic, mesencephalic, isthmic, accessory, and hypoglossal crest do not form ganglia. Cervical ganglion 1 is separated early from the neural crest and is not a Froriep ganglion. (7) The cranial ganglia derived from neural crest show a specific relationship to individual neuromeres, and rhombomeres are better landmarks than the otic primordium, which descends during stages 9–14. (8) Epipharyngeal placodes of the pharyngeal arches contribute to cranial ganglia, although that of arch 1 is not typical. (9) The neural crest from rhombomeres 6 and 7 that migrates to pharyngeal arch 3 and from there rostrad to the truncus arteriosus at stage 12 is identified here, for the first time in the human, as the cardiac crest. (10) The hypoglossal crest provides cells that accompany those of myotomes 1–4 and form the hypoglossal cell cord at stages 13 and 14. (11) The occipital crest, which is related to somites 1–4 in the human, differs from the spinal mainly in that it does not develop ganglia. (12) The occipital and spinal portions of the crest migrate dorsoventrad and appear to traverse the sclerotomes before the differentiation into loose and dense zones in the latter. (13) Embryonic examples of synophthalmia and anencephaly are cited to emphasize the role of the neural crest in the development of cranial ganglia and the skull. PMID:17848161

Early experience shapes vocal neural coding and perception in songbirds

PubMed Central

Woolley, Sarah M. N.

2012-01-01

Songbirds, like humans, are highly accomplished vocal learners. The many parallels between speech and birdsong and conserved features of mammalian and avian auditory systems have led to the emergence of the songbird as a model system for studying the perceptual mechanisms of vocal communication. Laboratory research on songbirds allows the careful control of early life experience and high-resolution analysis of brain function during vocal learning, production and perception. Here, I review what songbird studies have revealed about the role of early experience in the development of vocal behavior, auditory perception and the processing of learned vocalizations by auditory neurons. The findings of these studies suggest general principles for how exposure to vocalizations during development and into adulthood influences the perception of learned vocal signals. PMID:22711657

Impaired theta phase-resetting underlying auditory N1 suppression in chronic alcoholism.

PubMed

Fuentemilla, Lluis; Marco-Pallarés, Josep; Gual, Antoni; Escera, Carles; Polo, Maria Dolores; Grau, Carles

2009-02-18

It has been suggested that chronic alcoholism may lead to altered neural mechanisms related to inhibitory processes. Here, we studied auditory N1 suppression phenomena (i.e. amplitude reduction with repetitive stimuli) in chronic alcoholic patients as an early-stage information-processing brain function involving inhibition by the analysis of the N1 event-related potential and time-frequency computation (spectral power and phase-resetting). Our results showed enhanced neural theta oscillatory phase-resetting underlying N1 generation in suppressed N1 event-related potential. The present findings suggest that chronic alcoholism alters neural oscillatory synchrony dynamics at very early stages of information processing.

Hippocampal Contribution to Context Encoding across Development Is Disrupted following Early-Life Adversity.

PubMed

Lambert, Hilary K; Sheridan, Margaret A; Sambrook, Kelly A; Rosen, Maya L; Askren, Mary K; McLaughlin, Katie A

2017-02-15

Context can drastically influence responses to environmental stimuli. For example, a gunshot should provoke a different response at a public park than a shooting range. Little is known about how contextual processing and neural correlates change across human development or about individual differences related to early environmental experiences. Children ( N = 60; 8-19 years, 24 exposed to interpersonal violence) completed a context encoding task during fMRI scanning using a delayed match-to-sample design with neutral, happy, and angry facial cues embedded in realistic background scenes. Outside the scanner, participants completed a memory test for context-face pairings. Context memory and neural correlates of context encoding did not vary with age. Larger hippocampal volume was associated with better context memory. Posterior hippocampus was recruited during context encoding, and greater activation in this region predicted better memory for contexts paired with angry faces. Children exposed to violence had poor memory of contexts paired with angry faces, reduced hippocampal volume, and atypical neural recruitment on encoding trials with angry faces, including reduced hippocampal activation and greater functional connectivity between hippocampus and ventrolateral prefrontal cortex (vlPFC). Greater hippocampus-vlPFC connectivity was associated with worse memory for contexts paired with angry faces. Posterior hippocampus appears to support context encoding, a process that does not exhibit age-related variation from middle childhood to late adolescence. Exposure to dangerous environments in childhood is associated with poor context encoding in the presence of threat, likely due to greater vlPFC-dependent attentional narrowing on threat cues at the expense of hippocampus-dependent processing of the broader context. SIGNIFICANCE STATEMENT The ability to use context to guide reactions to environmental stimuli promotes flexible behavior. Remarkably little research has examined how contextual processing changes across development or about influences of the early environment. We provide evidence for posterior hippocampus involvement in context encoding in youth and lack of age-related variation from middle childhood to late adolescence. Children exposed to interpersonal violence exhibited poor memory of contexts paired with angry faces and atypical neural recruitment during context encoding in the presence of threatening facial cues. Heightened attention to threat following violence exposure may come at the expense of encoding contextual information, which may ultimately contribute to pathological fear expressed in safe contexts. Copyright © 2017 the authors 0270-6474/17/371925-10$15.00/0.

Oxytocin during Development: Possible Organizational Effects on Behavior.

PubMed

Miller, Travis V; Caldwell, Heather K

2015-01-01

Oxytocin (Oxt) is a neurohormone known for its physiological roles associated with lactation and parturition in mammals. Oxt can also profoundly influence mammalian social behaviors such as affiliative, parental, and aggressive behaviors. While the acute effects of Oxt signaling on adult behavior have been heavily researched in many species, including humans, the developmental effects of Oxt on the brain and behavior are just beginning to be explored. There is evidence that Oxt in early postnatal and peripubertal development, and perhaps during prenatal life, affects adult behavior by altering neural structure and function. However, the specific mechanisms by which this occurs remain unknown. Thus, this review will detail what is known about how developmental Oxt impacts behavior as well as explore the specific neurochemicals and neural substrates that are important to these behaviors.

Early neural disruption and auditory processing outcomes in rodent models: implications for developmental language disability

PubMed Central

Fitch, R. Holly; Alexander, Michelle L.; Threlkeld, Steven W.

2013-01-01

Most researchers in the field of neural plasticity are familiar with the “Kennard Principle,” which purports a positive relationship between age at brain injury and severity of subsequent deficits (plateauing in adulthood). As an example, a child with left hemispherectomy can recover seemingly normal language, while an adult with focal injury to sub-regions of left temporal and/or frontal cortex can suffer dramatic and permanent language loss. Here we present data regarding the impact of early brain injury in rat models as a function of type and timing, measuring long-term behavioral outcomes via auditory discrimination tasks varying in temporal demand. These tasks were created to model (in rodents) aspects of human sensory processing that may correlate—both developmentally and functionally—with typical and atypical language. We found that bilateral focal lesions to the cortical plate in rats during active neuronal migration led to worse auditory outcomes than comparable lesions induced after cortical migration was complete. Conversely, unilateral hypoxic-ischemic (HI) injuries (similar to those seen in premature infants and term infants with birth complications) led to permanent auditory processing deficits when induced at a neurodevelopmental point comparable to human “term,” but only transient deficits (undetectable in adulthood) when induced in a “preterm” window. Convergent evidence suggests that regardless of when or how disruption of early neural development occurs, the consequences may be particularly deleterious to rapid auditory processing (RAP) outcomes when they trigger developmental alterations that extend into subcortical structures (i.e., lower sensory processing stations). Collective findings hold implications for the study of behavioral outcomes following early brain injury as well as genetic/environmental disruption, and are relevant to our understanding of the neurologic risk factors underlying developmental language disability in human populations. PMID:24155699

Early life social stress induced changes in depression and anxiety associated neural pathways which are correlated with impaired maternal care.

PubMed

Murgatroyd, Christopher A; Peña, Catherine J; Podda, Giovanni; Nestler, Eric J; Nephew, Benjamin C

2015-08-01

Exposures to various types of early life stress can be robust predictors of the development of psychiatric disorders, including depression and anxiety. The objective of the current study was to investigate the roles of the translationally relevant targets of central vasopressin, oxytocin, ghrelin, orexin, glucocorticoid, and the brain-derived neurotrophic factor (BDNF) pathway in an early chronic social stress (ECSS) based rodent model of postpartum depression and anxiety. The present study reports novel changes in gene expression and extracellular signal related kinase (ERK) protein levels in the brains of ECSS exposed rat dams that display previously reported depressed maternal care and increased maternal anxiety. Decreases in oxytocin, orexin, and ERK proteins, increases in ghrelin receptor, glucocorticoid and mineralocorticoid receptor mRNA levels, and bidirectional changes in vasopressin underscore related work on the adverse long-term effects of early life stress on neural activity and plasticity, maternal behavior, responses to stress, and depression and anxiety-related behavior. The differences in gene and protein expression and robust correlations between expression and maternal care and anxiety support increased focus on these targets in animal and clinical studies of the adverse effects of early life stress, especially those focusing on depression and anxiety in mothers and the transgenerational effects of these disorders on offspring. Copyright © 2015 Elsevier B.V. All rights reserved.

Sensitivity of hiPSC-derived neural stem cells (NSC) to Pyrroloquinoline quinone depends on their developmental stage.

PubMed

Augustyniak, J; Lenart, J; Zychowicz, M; Lipka, G; Gaj, P; Kolanowska, M; Stepien, P P; Buzanska, L

2017-12-01

Pyrroloquinoline quinone (PQQ) is a factor influencing on the mitochondrial biogenesis. In this study the PQQ effect on viability, total cell number, antioxidant capacity, mitochondrial biogenesis and differentiation potential was investigated in human induced Pluripotent Stem Cells (iPSC) - derived: neural stem cells (NSC), early neural progenitors (eNP) and neural progenitors (NP). Here we demonstrated that sensitivity to PQQ is dependent upon its dose and neural stage of development. Induction of the mitochondrial biogenesis by PQQ at three stages of neural differentiation was evaluated at mtDNA, mRNA and protein level. Changes in NRF1, TFAM and PPARGC1A gene expression were observed at all developmental stages, but only at eNP were correlated with the statistically significant increase in the mtDNA copy numbers and enhancement of SDHA, COX-1 protein level. Thus, the "developmental window" of eNP for PQQ-evoked mitochondrial biogenesis is proposed. This effect was independent of high antioxidant capacity of PQQ, which was confirmed in all tested cell populations, regardless of the stage of hiPSC neural differentiation. Furthermore, a strong induction of GFAP, with down regulation of MAP2 gene expression upon PQQ treatment was observed. This indicates a possibility of shifting the balance of cell differentiation in the favor of astroglia, but more research is needed at this point. Copyright © 2017 Elsevier Ltd. All rights reserved.

Znf703, a novel target of Pax3 and Zic1, regulates hindbrain and neural crest development in Xenopus.

PubMed

Hong, Chang-Soo; Saint-Jeannet, Jean-Pierre

2017-12-01

The transcription factors Pax3 and Zic1 are critical to specify the neural plate border and to promote neural crest formation. In a microarray screen designed to identify genes regulated by Pax3 and Zic1 in Xenopus we isolated Znf703/Nlz1 a transcriptional repressor member of the NET (NocA/Nlz, Elbow, and TLP-1) protein family. At early neurula stage znf703 is expressed in the dorsal ectoderm, spanning the neural plate and neural plate border, with an anterior boundary of expression corresponding to rhombomeres 3 and 4 (r3/r4) in the prospective hindbrain. As a bonafide target of Pax3 and Zic1, znf703 is activated by neural plate border inducing signals, and its expression depends on Pax3 and Zic1 function in the embryo. Znf703 morpholino-mediated knockdown expanded several posterior hindbrain genes, while Znf703 overexpression completely obliterated the expression of these segmental genes, signifying that the transcriptional repressor activity of Znf703 is critical to pattern the hindbrain. Furthermore, snai2 and sox10 expression was severely impaired upon manipulation of Znf703 expression levels in the embryo suggesting that Znf703 participates in neural crest formation downstream of Pax3 and Zic1 in Xenopus. © 2017 Wiley Periodicals, Inc.

Converging on a core cognitive deficit: the impact of various neurodevelopmental insults on cognitive control

PubMed Central

O'Reilly, Kally C.; Kao, Hsin-Yi; Lee, Heekyung; Fenton, André A.

2014-01-01

Despite substantial effort and immense need, the treatment options for major neuropsychiatric illnesses like schizophrenia are limited and largely ineffective at improving the most debilitating cognitive symptoms that are central to mental illness. These symptoms include cognitive control deficits, the inability to selectively use information that is currently relevant and ignore what is currently irrelevant. Contemporary attempts to accelerate progress are in part founded on an effort to reconceptualize neuropsychiatric illness as a disorder of neural development. This neuro-developmental framework emphasizes abnormal neural circuits on the one hand, and on the other, it suggests there are therapeutic opportunities to exploit the developmental processes of excitatory neuron pruning, inhibitory neuron proliferation, elaboration of myelination, and other circuit refinements that extend through adolescence and into early adulthood. We have crafted a preclinical research program aimed at cognition failures that may be relevant to mental illness. By working with a variety of neurodevelopmental rodent models, we strive to identify a common pathophysiology that underlies cognitive control failure as well as a common strategy for improving cognition in the face of neural circuit abnormalities. Here we review our work to characterize cognitive control deficits in rats with a neonatal ventral hippocampus lesion and rats that were exposed to Methylazoxymethanol acetate (MAM) in utero. We review our findings as they pertain to early developmental processes, including neurogenesis, as well as the power of cognitive experience to refine neural circuit function within the mature and maturing brain's cognitive circuitry. PMID:24966811

Adverse early life environment increases hippocampal microglia abundance in conjunction with decreased neural stem cells in juvenile mice.

PubMed

Cohen, Susan; Ke, Xingrao; Liu, Qiuli; Fu, Qi; Majnik, Amber; Lane, Robert

2016-12-01

Adverse maternal lifestyle resulting in adverse early life environment (AELE) increases risks for neuropsychiatric disorders in offspring. Neuropsychiatric disorders are associated with impaired neurogenesis and neuro-inflammation in the hippocampus (HP). Microglia are neuro-inflammatory cells in the brain that regulate neurogenesis via toll-like receptors (TLR). TLR-9 is implicated in neurogenesis inhibition and is responsible for stress-related inflammatory responses. We hypothesized that AELE would increase microglia cell count and increase TLR-9 expression in juvenile mouse HP. These increases in microglia cell count and TLR-9 expression would be associated with decrease neural stem cell count and neuronal cell count. We developed a mouse model of AELE combining Western diet and a stress environment. Stress environment consisted of random change from embryonic day 13 (E13) to E17 as well as static change in maternal environment from E13 to postnatal day 21(P21). At P21, we measured hippocampal cell numbers of microglia, neural stem cell and neuron, as well as hippocampal TLR-9 expression. AELE significantly increased total microglia number and TLR-9 expression in the hippocampus. Concurrently, AELE significantly decreased neural stem cell and neuronal numbers. AELE increased the neuro-inflammatory cellular response in the juvenile HP. We speculate that increased neuro-inflammatory responses may contribute to impaired neurogenesis seen in this model. Copyright © 2016 ISDN. Published by Elsevier Ltd. All rights reserved.

Behavioral Inhibition and Developmental Risk: A Dual-Processing Perspective

PubMed Central

Henderson, Heather A; Pine, Daniel S; Fox, Nathan A

2015-01-01

Behavioral inhibition (BI) is an early-appearing temperament characterized by strong reactions to novelty. BI shows a good deal of stability over childhood and significantly increases the risk for later diagnosis of social anxiety disorder (SAD). Despite these general patterns, many children with high BI do not go on to develop clinical, or even subclinical, anxiety problems. Therefore, understanding the cognitive and neural bases of individual differences in developmental risk and resilience is of great importance. The present review is focused on the relation of BI to two types of information processing: automatic (novelty detection, attention biases to threat, and incentive processing) and controlled (attention shifting and inhibitory control). We propose three hypothetical models (Top-Down Model of Control; Risk Potentiation Model of Control; and Overgeneralized Control Model) linking these processes to variability in developmental outcomes for BI children. We argue that early BI is associated with an early bias to quickly and preferentially process information associated with motivationally salient cues. When this bias is strong and stable across development, the risk for SAD is increased. Later in development, children with a history of BI tend to display normative levels of performance on controlled attention tasks, but they demonstrate exaggerated neural responses in order to do so, which may further potentiate risk for anxiety-related problems. We conclude by discussing the reviewed studies with reference to the hypothetical models and make suggestions regarding future research and implications for treatment. PMID:25065499

Neural Language Processing in Adolescent First-Language Learners: Longitudinal Case Studies in American Sign Language

PubMed Central

Ferjan Ramirez, Naja; Leonard, Matthew K.; Davenport, Tristan S.; Torres, Christina; Halgren, Eric; Mayberry, Rachel I.

2016-01-01

One key question in neurolinguistics is the extent to which the neural processing system for language requires linguistic experience during early life to develop fully. We conducted a longitudinal anatomically constrained magnetoencephalography (aMEG) analysis of lexico-semantic processing in 2 deaf adolescents who had no sustained language input until 14 years of age, when they became fully immersed in American Sign Language. After 2 to 3 years of language, the adolescents' neural responses to signed words were highly atypical, localizing mainly to right dorsal frontoparietal regions and often responding more strongly to semantically primed words (Ferjan Ramirez N, Leonard MK, Torres C, Hatrak M, Halgren E, Mayberry RI. 2014. Neural language processing in adolescent first-language learners. Cereb Cortex. 24 (10): 2772–2783). Here, we show that after an additional 15 months of language experience, the adolescents' neural responses remained atypical in terms of polarity. While their responses to less familiar signed words still showed atypical localization patterns, the localization of responses to highly familiar signed words became more concentrated in the left perisylvian language network. Our findings suggest that the timing of language experience affects the organization of neural language processing; however, even in adolescence, language representation in the human brain continues to evolve with experience. PMID:25410427

C8orf46 homolog encodes a novel protein Vexin that is required for neurogenesis in Xenopus laevis.

PubMed

Moore, Kathryn B; Logan, Mary A; Aldiri, Issam; Roberts, Jacqueline M; Steele, Michael; Vetter, Monica L

2018-05-01

Neural basic helix-loop helix (bHLH) transcription factors promote progenitor cell differentiation by activation of downstream target genes that coordinate neuronal differentiation. Here we characterize a neural bHLH target gene in Xenopus laevis, vexin (vxn; previously sbt1), that is homologous to human c8orf46 and is conserved across vertebrate species. C8orf46 has been implicated in cancer progression, but its function is unknown. Vxn is transiently expressed in differentiating progenitors in the developing central nervous system (CNS), and is required for neurogenesis in the neural plate and retina. Its function is conserved, since overexpression of either Xenopus or mouse vxn expands primary neurogenesis and promotes early retinal cell differentiation in cooperation with neural bHLH factors. Vxn protein is localized to the cell membrane and the nucleus, but functions in the nucleus to promote neural differentiation. Vxn inhibits cell proliferation, and works with the cyclin-dependent kinase inhibitor p27Xic1 (cdkn1b) to enhance neurogenesis and increase levels of the proneural protein Neurog2. We propose that vxn provides a key link between neural bHLH activity and execution of the neurogenic program. Copyright © 2018 Elsevier Inc. All rights reserved.

Neural Connectivity Patterns Underlying Symbolic Number Processing Indicate Mathematical Achievement in Children

ERIC Educational Resources Information Center

Park, Joonkoo; Li, Rosa; Brannon, Elizabeth M.

2014-01-01

In early childhood, humans learn culturally specific symbols for number that allow them entry into the world of complex numerical thinking. Yet little is known about how the brain supports the development of the uniquely human symbolic number system. Here, we use functional magnetic resonance imaging along with an effective connectivity analysis…

Face Engagement during Infancy Predicts Later Face Recognition Ability in Younger Siblings of Children with Autism

ERIC Educational Resources Information Center

de Klerk, Carina C. J. M.; Gliga, Teodora; Charman, Tony; Johnson, Mark H.

2014-01-01

Face recognition difficulties are frequently documented in children with autism spectrum disorders (ASD). It has been hypothesized that these difficulties result from a reduced interest in faces early in life, leading to decreased cortical specialization and atypical development of the neural circuitry for face processing. However, a recent study…

Disruption of zebrafish cyclin G-associated kinase (GAK) function impairs the expression of Notch-dependent genes during neurogenesis and causes defects in neuronal development

PubMed Central

2010-01-01

Background The J-domain-containing protein auxilin, a critical regulator in clathrin-mediated transport, has been implicated in Drosophila Notch signaling. To ask if this role of auxilin is conserved and whether auxilin has additional roles in development, we have investigated the functions of auxilin orthologs in zebrafish. Results Like mammals, zebrafish has two distinct auxilin-like molecules, auxilin and cyclin G-associated kinase (GAK), differing in their domain structures and expression patterns. Both zebrafish auxilin and GAK can functionally substitute for the Drosophila auxilin, suggesting that they have overlapping molecular functions. Still, they are not completely redundant, as morpholino-mediated knockdown of the ubiquitously expressed GAK alone can increase the specification of neuronal cells, a known Notch-dependent process, and decrease the expression of Her4, a Notch target gene. Furthermore, inhibition of GAK function caused an elevated level of apoptosis in neural tissues, resulting in severe degeneration of neural structures. Conclusion In support of the notion that endocytosis plays important roles in Notch signaling, inhibition of zebrafish GAK function affects embryonic neuronal cell specification and Her4 expression. In addition, our analysis suggests that zebrafish GAK has at least two functions during the development of neural tissues: an early Notch-dependent role in neuronal patterning and a late role in maintaining the survival of neural cells. PMID:20082716

Disruption of Msx-1 and Msx-2 reveals roles for these genes in craniofacial, eye, and axial development.

PubMed

Foerst-Potts, L; Sadler, T W

1997-05-01

In mouse embryos, the muscle segment homeobox genes, Msx-1 and Msx-2 are expressed during critical stages of neural tube, neural crest, and craniofacial development, suggesting that these genes play important roles in organogenesis and cell differentiation. Although the patterns of expression are intriguing, little is known about the function of these genes in vertebrate embryonic development. Therefore, the expression of both genes, separately and together, was disrupted using antisense oligodeoxynucleotides and whole embryo culture techniques. Antisense attenuation of Msx-1 during early stages of neurulation produced hypoplasia of the maxillary, mandibular, and frontonasal prominences, eye anomalies, and somite and neural tube abnormalities. Eye defects consisted of enlarged optic vesicles, which may ultimately result in micropthalmia similar to that observed in Small eye mice homozygous for mutations in the Pax-6 gene. Histological sections and SEM analysis revealed a thinning of the neuroepithelium in the diencephalon and optic vesicle and mesenchymal deficiencies in the craniofacial region. Injections of Msx-2 antisense oligodeoxynucleotides produced similar malformations as those targeting Msx-1, with the exception that there was an increase in number and severity of neural tube and somite defects. Embryos injected with the combination of Msx-1 + Msx-2 antisense oligodeoxynucleotides showed no novel abnormalities, suggesting that the genes do not operate in a redundant manner.

Occipital cortical thickness in very low birth weight born adolescents predicts altered neural specialization of visual semantic category related neural networks.

PubMed

Klaver, Peter; Latal, Beatrice; Martin, Ernst

2015-01-01

Very low birth weight (VLBW) premature born infants have a high risk to develop visual perceptual and learning deficits as well as widespread functional and structural brain abnormalities during infancy and childhood. Whether and how prematurity alters neural specialization within visual neural networks is still unknown. We used functional and structural brain imaging to examine the visual semantic system of VLBW born (<1250 g, gestational age 25-32 weeks) adolescents (13-15 years, n = 11, 3 males) and matched term born control participants (13-15 years, n = 11, 3 males). Neurocognitive assessment revealed no group differences except for lower scores on an adaptive visuomotor integration test. All adolescents were scanned while viewing pictures of animals and tools and scrambled versions of these pictures. Both groups demonstrated animal and tool category related neural networks. Term born adolescents showed tool category related neural activity, i.e. tool pictures elicited more activity than animal pictures, in temporal and parietal brain areas. Animal category related activity was found in the occipital, temporal and frontal cortex. VLBW born adolescents showed reduced tool category related activity in the dorsal visual stream compared with controls, specifically the left anterior intraparietal sulcus, and enhanced animal category related activity in the left middle occipital gyrus and right lingual gyrus. Lower birth weight of VLBW adolescents correlated with larger thickness of the pericalcarine gyrus in the occipital cortex and smaller surface area of the superior temporal gyrus in the lateral temporal cortex. Moreover, larger thickness of the pericalcarine gyrus and smaller surface area of the superior temporal gyrus correlated with reduced tool category related activity in the parietal cortex. Together, our data suggest that very low birth weight predicts alterations of higher order visual semantic networks, particularly in the dorsal stream. The differences in neural specialization may be associated with aberrant cortical development of areas in the visual system that develop early in childhood. Copyright © 2014 Elsevier Ltd. All rights reserved.

Knowledge-Based Aircraft Automation: Managers Guide on the use of Artificial Intelligence for Aircraft Automation and Verification and Validation Approach for a Neural-Based Flight Controller

NASA Technical Reports Server (NTRS)

Broderick, Ron

1997-01-01

The ultimate goal of this report was to integrate the powerful tools of artificial intelligence into the traditional process of software development. To maintain the US aerospace competitive advantage, traditional aerospace and software engineers need to more easily incorporate the technology of artificial intelligence into the advanced aerospace systems being designed today. The future goal was to transition artificial intelligence from an emerging technology to a standard technology that is considered early in the life cycle process to develop state-of-the-art aircraft automation systems. This report addressed the future goal in two ways. First, it provided a matrix that identified typical aircraft automation applications conducive to various artificial intelligence methods. The purpose of this matrix was to provide top-level guidance to managers contemplating the possible use of artificial intelligence in the development of aircraft automation. Second, the report provided a methodology to formally evaluate neural networks as part of the traditional process of software development. The matrix was developed by organizing the discipline of artificial intelligence into the following six methods: logical, object representation-based, distributed, uncertainty management, temporal and neurocomputing. Next, a study of existing aircraft automation applications that have been conducive to artificial intelligence implementation resulted in the following five categories: pilot-vehicle interface, system status and diagnosis, situation assessment, automatic flight planning, and aircraft flight control. The resulting matrix provided management guidance to understand artificial intelligence as it applied to aircraft automation. The approach taken to develop a methodology to formally evaluate neural networks as part of the software engineering life cycle was to start with the existing software quality assurance standards and to change these standards to include neural network development. The changes were to include evaluation tools that can be applied to neural networks at each phase of the software engineering life cycle. The result was a formal evaluation approach to increase the product quality of systems that use neural networks for their implementation.

Zebrafish zic2 controls formation of periocular neural crest and choroid fissure morphogenesis.

PubMed

Sedykh, Irina; Yoon, Baul; Roberson, Laura; Moskvin, Oleg; Dewey, Colin N; Grinblat, Yevgenya

2017-09-01

The vertebrate retina develops in close proximity to the forebrain and neural crest-derived cartilages of the face and jaw. Coloboma, a congenital eye malformation, is associated with aberrant forebrain development (holoprosencephaly) and with craniofacial defects (frontonasal dysplasia) in humans, suggesting a critical role for cross-lineage interactions during retinal morphogenesis. ZIC2, a zinc-finger transcription factor, is linked to human holoprosencephaly. We have previously used morpholino assays to show zebrafish zic2 functions in the developing forebrain, retina and craniofacial cartilage. We now report that zebrafish with genetic lesions in zebrafish zic2 orthologs, zic2a and zic2b, develop with retinal coloboma and craniofacial anomalies. We demonstrate a requirement for zic2 in restricting pax2a expression and show evidence that zic2 function limits Hh signaling. RNA-seq transcriptome analysis identified an early requirement for zic2 in periocular neural crest as an activator of alx1, a transcription factor with essential roles in craniofacial and ocular morphogenesis in human and zebrafish. Collectively, these data establish zic2 mutant zebrafish as a powerful new genetic model for in-depth dissection of cell interactions and genetic controls during craniofacial complex development. Copyright © 2017 Elsevier Inc. All rights reserved.

Developmental regulation of fear learning and anxiety behavior by endocannabinoids.

PubMed

Lee, T T-Y; Hill, M N; Lee, F S

2016-01-01

The developing brain undergoes substantial maturation into adulthood and the development of specific neural structures occurs on differing timelines. Transient imbalances between developmental trajectories of corticolimbic structures, which are known to contribute to regulation over fear learning and anxiety, can leave an individual susceptible to mental illness, particularly anxiety disorders. There is a substantial body of literature indicating that the endocannabinoid (eCB) system critically regulates stress responsivity and emotional behavior throughout the life span, making this system a novel therapeutic target for stress- and anxiety-related disorders. During early life and adolescence, corticolimbic eCB signaling changes dynamically and coincides with different sensitive periods of fear learning, suggesting that eCB signaling underlies age-specific fear learning responses. Moreover, perturbations to these normative fluctuations in corticolimbic eCB signaling, such as stress or cannabinoid exposure, could serve as a neural substrate contributing to alterations to the normative developmental trajectory of neural structures governing emotional behavior and fear learning. In this review, we first introduce the components of the eCB system and discuss clinical and rodent models showing eCB regulation of fear learning and anxiety in adulthood. Next, we highlight distinct fear learning and regulation profiles throughout development and discuss the ontogeny of the eCB system in the central nervous system, and models of pharmacological augmentation of eCB signaling during development in the context of fear learning and anxiety. © 2015 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

The development of cortical connections.

PubMed

Price, David J; Kennedy, Henry; Dehay, Colette; Zhou, Libing; Mercier, Marjorie; Jossin, Yves; Goffinet, André M; Tissir, Fadel; Blakey, Daniel; Molnár, Zoltán

2006-02-01

The cortex receives its major sensory input from the thalamus via thalamocortical axons, and cortical neurons are interconnected in complex networks by corticocortical and callosal axons. Our understanding of the mechanisms generating the circuitry that confers functional properties on cortical neurons and networks, although poor, has been advanced significantly by recent research on the molecular mechanisms of thalamocortical axonal guidance and ordering. Here we review recent advances in knowledge of how thalamocortical axons are guided and how they maintain order during that process. Several studies have shown the importance in this process of guidance molecules including Eph receptors and ephrins, members of the Wnt signalling pathway and members of a novel planar cell polarity pathway. Signalling molecules and transcription factors expressed with graded concentrations across the cortex are important in establishing cortical maps of the topography of sensory surfaces. Neural activity, both spontaneous and evoked, plays a role in refining thalamocortical connections but recent work has indicated that neural activity is less important than was previously thought for the development of some early maps. A strategy used widely in the development of corticocortical and callosal connections is the early overproduction of projections followed by selection after contact with the target structure. Here we discuss recent work in primates indicating that elimination of juvenile projections is not a major mechanism in the development of pathways feeding information forward to higher levels of cortical processing, although its use is common to developing feedback pathways.

Neural crest apoptosis and the establishment of craniofacial pattern: an honorable death.

PubMed

Graham, A; Koentges, G; Lumsden, A

1996-01-01

During development of the vertebrate head neural crest cells emigrate from the hindbrain and populate the branchial arches, giving rise to distinct skeletal elements and muscle connective tissues in each arch. The production of neural crest from the hindbrain is discontinuous and crest cells destined for different arches, carrying different positional cues, are separated by regions of apoptosis centered on rhombomeres (r) 3 and r5. This cell death program is under the interactive control of the neighboring hindbrain segments. Both r3 and r5 produce large numbers of crest cells when freed from their flanking rhombomere, but when conjoined with their neighbor the cell death program is restored. Two key components of this program are Bmp 4 and msx-2, both of which are expressed in the apoptotic foci of r3 and r5 and which are also regulated by neighbor interactions. Importantly, the addition of recombinant Bmp 4 to isolated cultures of r3 and r5 induces the expression of Bmp 4 and msx-2 and restores the cell death program. This early neural crest segregation is maintained during development and it has profound effects upon the final craniofacial pattern. Even though crest cells from different axial origins will contribute to compound skeletal elements, these distinct populations do not intermingle. Furthermore head muscle connective tissues are exclusively anchored to skeletal domains arising from neural crest from the same axial level. Thus the discontinuous production of neural crest sculpts the crest into nonmixing streams and consequently ensures the fidelity of patterning.

Selective Roles of Normal and Mutant Huntingtin in Neural Induction and Early Neurogenesis

PubMed Central

Nguyen, Giang D.; Gokhan, Solen; Molero, Aldrin E.; Mehler, Mark F.

2013-01-01

Huntington's disease (HD) is a neurodegenerative disorder caused by abnormal polyglutamine expansion in the amino-terminal end of the huntingtin protein (Htt) and characterized by progressive striatal and cortical pathology. Previous reports have shown that Htt is essential for embryogenesis, and a recent study by our group revealed that the pathogenic form of Htt (mHtt) causes impairments in multiple stages of striatal development. In this study, we have examined whether HD-associated striatal developmental deficits are reflective of earlier maturational alterations occurring at the time of neurulation by assessing differential roles of Htt and mHtt during neural induction and early neurogenesis using an in vitro mouse embryonic stem cell (ESC) clonal assay system. We demonstrated that the loss of Htt in ESCs (KO ESCs) severely disrupts the specification of primitive and definitive neural stem cells (pNSCs, dNSCs, respectively) during the process of neural induction. In addition, clonally derived KO pNSCs and dNSCs displayed impaired proliferative potential, enhanced cell death and altered multi-lineage potential. Conversely, as observed in HD knock-in ESCs (Q111 ESCs), mHtt enhanced the number and size of pNSC clones, which exhibited enhanced proliferative potential and precocious neuronal differentiation. The transition from Q111 pNSCs to fibroblast growth factor 2 (FGF2)-responsive dNSCs was marked by potentiation in the number of dNSCs and altered proliferative potential. The multi-lineage potential of Q111 dNSCs was also enhanced with precocious neurogenesis and oligodendrocyte progenitor elaboration. The generation of Q111 epidermal growth factor (EGF)-responsive dNSCs was also compromised, whereas their multi-lineage potential was unaltered. These abnormalities in neural induction were associated with differential alterations in the expression profiles of Notch, Hes1 and Hes5. These cumulative observations indicate that Htt is required for multiple stages of neural induction, whereas mHtt enhances this process and promotes precocious neurogenesis and oligodendrocyte progenitor cell elaboration. PMID:23691206

Angiogenesis in the Developing Spinal Cord: Blood Vessel Exclusion from Neural Progenitor Region Is Mediated by VEGF and Its Antagonists

PubMed Central

Takahashi, Teruaki; Takase, Yuta; Yoshino, Takashi; Saito, Daisuke; Tadokoro, Ryosuke; Takahashi, Yoshiko

2015-01-01

Blood vessels in the central nervous system supply a considerable amount of oxygen via intricate vascular networks. We studied how the initial vasculature of the spinal cord is formed in avian (chicken and quail) embryos. Vascular formation in the spinal cord starts by the ingression of intra-neural vascular plexus (INVP) from the peri-neural vascular plexus (PNVP) that envelops the neural tube. At the ventral region of the PNVP, the INVP grows dorsally in the neural tube, and we observed that these vessels followed the defined path at the interface between the medially positioned and undifferentiated neural progenitor zone and the laterally positioned differentiated zone. When the interface between these two zones was experimentally displaced, INVP faithfully followed a newly formed interface, suggesting that the growth path of the INVP is determined by surrounding neural cells. The progenitor zone expressed mRNA of vascular endothelial growth factor-A whereas its receptor VEGFR2 and FLT-1 (VEGFR1), a decoy for VEGF, were expressed in INVP. By manipulating the neural tube with either VEGF or the soluble form of FLT-1, we found that INVP grew in a VEGF-dependent manner, where VEGF signals appear to be fine-tuned by counteractions with anti-angiogenic activities including FLT-1 and possibly semaphorins. These results suggest that the stereotypic patterning of early INVP is achieved by interactions between these vessels and their surrounding neural cells, where VEGF and its antagonists play important roles. PMID:25585380

Differentiation and Cell-Cell Interactions of Neural Progenitor Cells Transplanted into Intact Adult Brain.

PubMed

Sukhinich, K K; Kosykh, A V; Aleksandrova, M A

2015-11-01

We studied the behavior and cell-cell interactions of embryonic brain cell from GFP-reporter mice after their transplantation into the intact adult brain. Fragments or cell suspensions of fetal neocortical cells at different stages of development were transplanted into the neocortex and striatum of adult recipients. Even in intact brain, the processes of transplanted neurons formed extensive networks in the striatum and neocortical layers I and V-VI. Processes of transplanted cells at different stages of development attained the rostral areas of the frontal cortex and some of them reached the internal capsule. However, the cells transplanted in suspension had lower process growth potency than cells from tissue fragments. Tyrosine hydroxylase fibers penetrated from the recipient brain into grafts at both early and late stages of development. Our experiments demonstrated the formation of extensive reciprocal networks between the transplanted fetal neural cells and recipient brain neurons even in intact brain.

Infant Visual Attention and Object Recognition

PubMed Central

Reynolds, Greg D.

2015-01-01

This paper explores the role visual attention plays in the recognition of objects in infancy. Research and theory on the development of infant attention and recognition memory are reviewed in three major sections. The first section reviews some of the major findings and theory emerging from a rich tradition of behavioral research utilizing preferential looking tasks to examine visual attention and recognition memory in infancy. The second section examines research utilizing neural measures of attention and object recognition in infancy as well as research on brain-behavior relations in the early development of attention and recognition memory. The third section addresses potential areas of the brain involved in infant object recognition and visual attention. An integrated synthesis of some of the existing models of the development of visual attention is presented which may account for the observed changes in behavioral and neural measures of visual attention and object recognition that occur across infancy. PMID:25596333

The historical development of neuroscience in physical rehabilitation.

PubMed

Cohen, H; Reed, K L

1996-01-01

Neuroscience and occupational therapy in physical rehabilitation have developed along parallel tracks. As physicians began to study the neural bases of motor control, they also began to reconsider the sequelae of "hopeless" diagnoses as conditions that they could influence. This change in some physicians' understanding of the neural mechanisms of motor control influenced other clinicians' ideas about patient care. Early work on treatment of patients with cerebral palsy and polio led to improvements in treatment approaches used to facilitate motor skill and functional motor ability in patients with upper motor neuron disorders. From the 1950s to the present, therapists have refined their treatment techniques as knowledge from neuroscience has become available. A few therapists, who are gradually increasing in number, have turned to the laboratory to study basic neuroscience problems that affect clinical treatment. This article describes the development of neuroscience research and neurorehabilitation theories and indicates common themes.

Frodo proteins: modulators of Wnt signaling in vertebrate development.

PubMed

Brott, Barbara K; Sokol, Sergei Y

2005-09-01

The Frodo/dapper (Frd) proteins are recently discovered signaling adaptors, which functionally and physically interact with Wnt and Nodal signaling pathways during vertebrate development. The Frd1 and Frd2 genes are expressed in dynamic patterns in early embryos, frequently in cells undergoing epithelial-mesenchymal transition. The Frd proteins function in multiple developmental processes, including mesoderm and neural tissue specification, early morphogenetic cell movements, and organogenesis. Loss-of-function studies using morpholino antisense oligonucleotides demonstrate that the Frd proteins regulate Wnt signal transduction in a context-dependent manner and may be involved in Nodal signaling. The identification of Frd-associated factors and cellular targets of the Frd proteins should shed light on the molecular mechanisms underlying Frd functions in embryonic development and in cancer.

Does modulation of selective attention to features reflect enhancement or suppression of neural activity?

PubMed

Daffner, Kirk R; Zhuravleva, Tatyana Y; Sun, Xue; Tarbi, Elise C; Haring, Anna E; Rentz, Dorene M; Holcomb, Phillip J

2012-02-01

Numerous studies have demonstrated that selective attention to color is associated with a larger neural response under attend than ignore conditions, but have not addressed whether this difference reflects enhanced activity under attend or suppressed activity under ignore. In this study, a color-neutral condition was included, which presented stimuli physically identical to those under attend and ignore conditions, but in which color was not task relevant. Attention to color did not modulate the early sensory-evoked P1 and N1 components. Traditional ERP markers of early selection (the anterior Selection Positivity and posterior Selection Negativity) did not differ between the attend and neutral conditions, arguing against a mechanism of enhanced activity. However, there were markedly reduced responses under the ignore relative to the neutral condition, consistent with the view that early selection mechanisms reflect suppression of neural activity under the ignore condition. Copyright © 2011 Elsevier B.V. All rights reserved.

Heightened extended amygdala metabolism following threat characterizes the early phenotypic risk to develop anxiety-related psychopathology

PubMed Central

Shackman, Alexander J.; Fox, Andrew S.; Oler, Jonathan A.; Shelton, Steven E.; Oakes, Terrence R.; Davidson, Richard J.; Kalin, Ned H.

2016-01-01

Children with an anxious temperament (AT) are prone to heightened shyness and behavioral inhibition (BI). When chronic and extreme, this anxious, inhibited phenotype is an important early-life risk factor for the development of anxiety disorders, depression, and co-morbid substance abuse. Individuals with extreme AT often show persistent distress in the absence of immediate threat and this contextually inappropriate anxiety predicts future symptom development. Despite its clear clinical relevance, the neural circuitry governing the maladaptive persistence of anxiety remains unknown. Here, we used a well-established nonhuman primate model of childhood temperament and high-resolution 18fluorodeoxyglucose positron emission tomography (FDG-PET) imaging to understand the neural systems governing persistent anxiety and clarify their relevance to early-life phenotypic risk. We focused on BI, a core component of anxious temperament, because it affords the moment-by-moment temporal resolution needed to assess contextually appropriate and inappropriate anxiety. From a pool of 109 peri-adolescent rhesus monkeys, we formed groups characterized by high or low levels of BI, as indexed by freezing in response to an unfamiliar human intruder’s profile. The High-BI group showed consistently elevated signs of anxiety and wariness across more than 2 years of assessments. At the time of brain imaging, 1.5 years after initial phenotyping, the High-BI group showed persistently elevated freezing during a 30-min ‘recovery’ period following an encounter with the intruder — more than an order of magnitude greater than the Low-BI group — and this was associated with increased metabolism in the bed nucleus of the stria terminalis, a key component of the central extended amygdala. These observations provide a neurobiological framework for understanding the early phenotypic risk to develop anxiety-related psychopathology, for accelerating the development of improved interventions, and for understanding the origins of childhood temperament. PMID:27573879

Early oestrogens in shaping reproductive networks: evidence for a potential organisational role of oestradiol in female brain development.

PubMed

Bakker, J; Brock, O

2010-07-01

A central tenet of contemporary theories on mammalian brain and behavioural sexual differentiation is that an organisational action of testosterone, secreted by the male's testes, controls male-typical aspects of brain and behavioural development, whereas no active perinatal sex hormone signalling is required for female-typical sexual differentiation. Furthermore, the available evidence suggests that many, although not all, of the perinatal organisational actions of testosterone on the development of the male brain result from the cellular effects of oestradiol formed via neural aromatisation of testosterone. However, a default developmental programme for the female brain has been criticised. Indeed, we review new results obtained in aromatase knockout mice indicating that oestradiol actively contributes to the differentiation of female-typical aspects of brain and behavioural sexual differentiation. Furthermore, we propose that male-typical neural and behavioural differentiation occurs prenatally in genetic males under the influence of oestradiol, which is avoided in foetal genetic females by the neuroprotective actions of alpha-fetoprotein, whereas female-typical neural and behavioural differentiation normally occurs postnatally in genetic females under the influence of oestradiol that is presumably produced by the ovaries.

Quantitative Analysis of Cell Migration Using Optical Flow

PubMed Central

Boric, Katica; Orio, Patricio; Viéville, Thierry; Whitlock, Kathleen

2013-01-01

Neural crest cells exhibit dramatic migration behaviors as they populate their distant targets. Using a line of zebrafish expressing green fluorescent protein (sox10:EGFP) in neural crest cells we developed an assay to analyze and quantify cell migration as a population, and use it here to characterize in detail the subtle defects in cell migration caused by ethanol exposure during early development. The challenge was to quantify changes in the in vivo migration of all Sox10:EGFP expressing cells in the visual field of time-lapse movies. To perform this analysis we used an Optical Flow algorithm for motion detection and combined the analysis with a fit to an affine transformation. Through this analysis we detected and quantified significant differences in the cell migrations of Sox10:EGFP positive cranial neural crest populations in ethanol treated versus untreated embryos. Specifically, treatment affected migration by increasing the left-right asymmetry of the migrating cells and by altering the direction of cell movements. Thus, by applying this novel computational analysis, we were able to quantify the movements of populations of cells, allowing us to detect subtle changes in cell behaviors. Because cranial neural crest cells contribute to the formation of the frontal mass these subtle differences may underlie commonly observed facial asymmetries in normal human populations. PMID:23936049

Shared neural substrates for song discrimination in parental and parasitic songbirds.

PubMed

Louder, Matthew I M; Voss, Henning U; Manna, Thomas J; Carryl, Sophia S; London, Sarah E; Balakrishnan, Christopher N; Hauber, Mark E

2016-05-27

In many social animals, early exposure to conspecific stimuli is critical for the development of accurate species recognition. Obligate brood parasitic songbirds, however, forego parental care and young are raised by heterospecific hosts in the absence of conspecific stimuli. Having evolved from non-parasitic, parental ancestors, how brood parasites recognize their own species remains unclear. In parental songbirds (e.g. zebra finch Taeniopygia guttata), the primary and secondary auditory forebrain areas are known to be critical in the differential processing of conspecific vs. heterospecific songs. Here we demonstrate that the same auditory brain regions underlie song discrimination in adult brood parasitic pin-tailed whydahs (Vidua macroura), a close relative of the zebra finch lineage. Similar to zebra finches, whydahs showed stronger behavioral responses during conspecific vs. heterospecific song and tone pips as well as increased neural responses within the auditory forebrain, as measured by both functional magnetic resonance imaging (fMRI) and immediate early gene (IEG) expression. Given parallel behavioral and neuroanatomical patterns of song discrimination, our results suggest that the evolutionary transition to brood parasitism from parental songbirds likely involved an "evolutionary tinkering" of existing proximate mechanisms, rather than the wholesale reworking of the neural substrates of species recognition. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

ARGALI: an automatic cup-to-disc ratio measurement system for glaucoma detection and AnaLysIs framework

NASA Astrophysics Data System (ADS)

Liu, J.; Wong, D. W. K.; Lim, J. H.; Li, H.; Tan, N. M.; Wong, T. Y.

2009-02-01

Glaucoma is an irreversible ocular disease leading to permanent blindness. However, early detection can be effective in slowing or halting the progression of the disease. Physiologically, glaucoma progression is quantified by increased excavation of the optic cup. This progression can be quantified in retinal fundus images via the optic cup to disc ratio (CDR), since in increased glaucomatous neuropathy, the relative size of the optic cup to the optic disc is increased. The ARGALI framework constitutes of various segmentation approaches employing level set, color intensity thresholds and ellipse fitting for the extraction of the optic cup and disc from retinal images as preliminary steps. Following this, different combinations of the obtained results are then utilized to calculate the corresponding CDR values. The individual results are subsequently fused using a neural network. The learning function of the neural network is trained with a set of 100 retinal images For testing, a separate set 40 images is then used to compare the obtained CDR against a clinically graded CDR, and it is shown that the neural network-based result performs better than the individual components, with 96% of the results within intra-observer variability. The results indicate good promise for the further development of ARGALI as a tool for the early detection of glaucoma.

Large-scale generation of human iPSC-derived neural stem cells/early neural progenitor cells and their neuronal differentiation.

PubMed

D'Aiuto, Leonardo; Zhi, Yun; Kumar Das, Dhanjit; Wilcox, Madeleine R; Johnson, Jon W; McClain, Lora; MacDonald, Matthew L; Di Maio, Roberto; Schurdak, Mark E; Piazza, Paolo; Viggiano, Luigi; Sweet, Robert; Kinchington, Paul R; Bhattacharjee, Ayantika G; Yolken, Robert; Nimgaonka, Vishwajit L; Nimgaonkar, Vishwajit L

2014-01-01

Induced pluripotent stem cell (iPSC)-based technologies offer an unprecedented opportunity to perform high-throughput screening of novel drugs for neurological and neurodegenerative diseases. Such screenings require a robust and scalable method for generating large numbers of mature, differentiated neuronal cells. Currently available methods based on differentiation of embryoid bodies (EBs) or directed differentiation of adherent culture systems are either expensive or are not scalable. We developed a protocol for large-scale generation of neuronal stem cells (NSCs)/early neural progenitor cells (eNPCs) and their differentiation into neurons. Our scalable protocol allows robust and cost-effective generation of NSCs/eNPCs from iPSCs. Following culture in neurobasal medium supplemented with B27 and BDNF, NSCs/eNPCs differentiate predominantly into vesicular glutamate transporter 1 (VGLUT1) positive neurons. Targeted mass spectrometry analysis demonstrates that iPSC-derived neurons express ligand-gated channels and other synaptic proteins and whole-cell patch-clamp experiments indicate that these channels are functional. The robust and cost-effective differentiation protocol described here for large-scale generation of NSCs/eNPCs and their differentiation into neurons paves the way for automated high-throughput screening of drugs for neurological and neurodegenerative diseases.

Intercellular crosstalk in human malignant melanoma.

PubMed

Dvořánková, Barbora; Szabo, Pavol; Kodet, Ondřej; Strnad, Hynek; Kolář, Michal; Lacina, Lukáš; Krejčí, Eliška; Naňka, Ondřej; Šedo, Aleksi; Smetana, Karel

2017-05-01

Incidence of malignant melanoma is increasing globally. While the initial stages of tumors can be easily treated by a simple surgery, the therapy of advanced stages is rather limited. Melanoma cells spread rapidly through the body of a patient to form multiple metastases. Consequently, the survival rate is poor. Therefore, emphasis in melanoma research is given on early diagnosis and development of novel and more potent therapeutic options. The malignant melanoma is arising from melanocytes, cells protecting mitotically active keratinocytes against damage caused by UV light irradiation. The melanocytes originate in the neural crest and consequently migrate to the epidermis. The relationship between the melanoma cells, the melanocytes, and neural crest stem cells manifests when the melanoma cells are implanted to an early embryo: they use similar migratory routes as the normal neural crest cells. Moreover, malignant potential of these melanoma cells is overdriven in this experimental model, probably due to microenvironmental reprogramming. This observation demonstrates the crucial role of the microenvironment in melanoma biology. Indeed, malignant tumors in general represent complex ecosystems, where multiple cell types influence the growth of genetically mutated cancer cells. This concept is directly applicable to the malignant melanoma. Our review article focuses on possible strategies to modify the intercellular crosstalk in melanoma that can be employed for therapeutic purposes.

An Integrative Model for the Neural Mechanism of Eye Movement Desensitization and Reprocessing (EMDR).

PubMed

Coubard, Olivier A

2016-01-01

Since the seminal report by Shapiro that bilateral stimulation induces cognitive and emotional changes, 26 years of basic and clinical research have examined the effects of Eye Movement Desensitization and Reprocessing (EMDR) in anxiety disorders, particularly in post-traumatic stress disorder (PTSD). The present article aims at better understanding EMDR neural mechanism. I first review procedural aspects of EMDR protocol and theoretical hypothesis about EMDR effects, and develop the reasons why the scientific community is still divided about EMDR. I then slide from psychology to physiology describing eye movements/emotion interaction from the physiological viewpoint, and introduce theoretical and technical tools used in movement research to re-examine EMDR neural mechanism. Using a recent physiological model for the neuropsychological architecture of motor and cognitive control, the Threshold Interval Modulation with Early Release-Rate of rIse Deviation with Early Release (TIMER-RIDER)-model, I explore how attentional control and bilateral stimulation may participate to EMDR effects. These effects may be obtained by two processes acting in parallel: (i) activity level enhancement of attentional control component; and (ii) bilateral stimulation in any sensorimotor modality, both resulting in lower inhibition enabling dysfunctional information to be processed and anxiety to be reduced. The TIMER-RIDER model offers quantitative predictions about EMDR effects for future research about its underlying physiological mechanisms.

Atypical neural responses to vocal anger in attention-deficit/hyperactivity disorder.

PubMed

Chronaki, Georgia; Benikos, Nicholas; Fairchild, Graeme; Sonuga-Barke, Edmund J S

2015-04-01

Deficits in facial emotion processing, reported in attention-deficit/hyperactivity disorder (ADHD), have been linked to both early perceptual and later attentional components of event-related potentials (ERPs). However, the neural underpinnings of vocal emotion processing deficits in ADHD have yet to be characterised. Here, we report the first ERP study of vocal affective prosody processing in ADHD. Event-related potentials of 6-11-year-old children with ADHD (n = 25) and typically developing controls (n = 25) were recorded as they completed a task measuring recognition of vocal prosodic stimuli (angry, happy and neutral). Audiometric assessments were conducted to screen for hearing impairments. Children with ADHD were less accurate than controls at recognising vocal anger. Relative to controls, they displayed enhanced N100 and attenuated P300 components to vocal anger. The P300 effect was reduced, but remained significant, after controlling for N100 effects by rebaselining. Only the N100 effect was significant when children with ADHD and comorbid conduct disorder (n = 10) were excluded. This study provides the first evidence linking ADHD to atypical neural activity during the early perceptual stages of vocal anger processing. These effects may reflect preattentive hyper-vigilance to vocal anger in ADHD. © 2014 Association for Child and Adolescent Mental Health.

Brain activity and infant attachment history in young men during loss and reward processing.

PubMed

Quevedo, Karina; Waters, Theodore E A; Scott, Hannah; Roisman, Glenn I; Shaw, Daniel S; Forbes, Erika E

2017-05-01

There is now ample evidence that the quality of early attachment experiences shapes expectations for supportive and responsive care and ultimately serves to scaffold adaptation to the salient tasks of development. Nonetheless, few studies have identified neural mechanisms that might give rise to these associations. Using a moderately large sample of low-income male participants recruited during infancy (N = 171), we studied the predictive significance of attachment insecurity and disorganization at age 18 months (as measured in the Strange Situation Procedure) for patterns of neural activation to reward and loss at age 20 years (assessed during a reward-based task as part of a functional magnetic resonance imaging scan). Results indicated that individuals with a history of insecure attachment showed hyperactivity in (a) reward- and emotion-related (e.g., basal ganglia and amygdala) structures and (b) emotion regulation and self-referential processing (cortical midline structures) in response to positive and negative outcomes (and anticipation of those outcomes). Further, the neural activation of individuals with a history of disorganized attachment suggested that they had greater emotional reactivity in anticipation of reward and employed greater cognitive control when negative outcomes were encountered. Overall, results suggest that the quality of early attachments has lasting impacts on brain function and reward processing.

The cognitive and neural correlates of psychopathy and especially callous-unemotional traits in youths: a systematic review of the evidence.

PubMed

Herpers, Pierre C M; Scheepers, Floor E; Bons, Daniëlle M A; Buitelaar, Jan K; Rommelse, Nanda N J

2014-02-01

It is unclear whether the concepts and findings of the underlying neurobiology of adult psychopathy apply to youths as well. If so, a life span approach to treatment should be taken. Because youths' brains are still developing, interventions at an early age may be far more effective in the long run. The aim of this systematic review is to examine whether the neurocognitive and neurobiological factors that underlie juvenile psychopathy, and specifically callous-unemotional (CU) traits, are similar to those underlying adult psychopathy. The results show that youths with CU traits show lower levels of prosocial reasoning, lower emotional responsivity, and decreased harm avoidance. Brain imaging studies in youths with CU traits are still rare. Available studies suggest specific neural correlates, such as a reduced response of the amygdala and a weaker functional connectivity between the amygdala and the ventromedial prefrontal cortex. These findings are largely in line with existing theories of adult psychopathy, such as the dual-hormone serotonergic hypothesis and the integrated emotions systems theory. We recommend that future studies investigate the role of oxytocin, invest in the study of neural mechanisms, and study the precursors, risk factors, and correlates of CU traits in early infancy and in longitudinal designs.

Confocal imaging of whole vertebrate embryos reveals novel insights into molecular and cellular mechanisms of organ development

NASA Astrophysics Data System (ADS)

Hadel, Diana M.; Keller, Bradley B.; Sandell, Lisa L.

2014-03-01

Confocal microscopy has been an invaluable tool for studying cellular or sub-cellular biological processes. The study of vertebrate embryology is based largely on examination of whole embryos and organs. The application of confocal microscopy to immunostained whole mount embryos, combined with three dimensional (3D) image reconstruction technologies, opens new avenues for synthesizing molecular, cellular and anatomical analysis of vertebrate development. Optical cropping of the region of interest enables visualization of structures that are morphologically complex or obscured, and solid surface rendering of fluorescent signal facilitates understanding of 3D structures. We have applied these technologies to whole mount immunostained mouse embryos to visualize developmental morphogenesis of the mammalian inner ear and heart. Using molecular markers of neuron development and transgenic reporters of neural crest cell lineage we have examined development of inner ear neurons that originate from the otic vesicle, along with the supporting glial cells that derive from the neural crest. The image analysis reveals a previously unrecognized coordinated spatial organization between migratory neural crest cells and neurons of the cochleovestibular nerve. The images also enable visualization of early cochlear spiral nerve morphogenesis relative to the developing cochlea, demonstrating a heretofore unknown association of neural crest cells with extending peripheral neurite projections. We performed similar analysis of embryonic hearts in mouse and chick, documenting the distribution of adhesion molecules during septation of the outflow tract and remodeling of aortic arches. Surface rendering of lumen space defines the morphology in a manner similar to resin injection casting and micro-CT.

Self-referenced processing, neurodevelopment and joint attention in autism.

PubMed

Mundy, Peter; Gwaltney, Mary; Henderson, Heather

2010-09-01

This article describes a parallel and distributed processing model (PDPM) of joint attention, self-referenced processing and autism. According to this model, autism involves early impairments in the capacity for rapid, integrated processing of self-referenced (proprioceptive and interoceptive) and other-referenced (exteroceptive) information. Measures of joint attention have proven useful in research on autism because they are sensitive to the early development of the 'parallel' and integrated processing of self- and other-referenced stimuli. Moreover, joint attention behaviors are a consequence, but also an organizer of the functional development of a distal distributed cortical system involving anterior networks including the prefrontal and insula cortices, as well as posterior neural networks including the temporal and parietal cortices. Measures of joint attention provide early behavioral indicators of atypical development in this parallel and distributed processing system in autism. In addition it is proposed that an early, chronic disturbance in the capacity for integrating self- and other-referenced information may have cascading effects on the development of self awareness in autism. The assumptions, empirical support and future research implications of this model are discussed.

Two distinct mechanisms silence chinmo in Drosophila neuroblasts and neuroepithelial cells to limit their self-renewal.

PubMed

Dillard, Caroline; Narbonne-Reveau, Karine; Foppolo, Sophie; Lanet, Elodie; Maurange, Cédric

2018-01-25

Whether common principles regulate the self-renewing potential of neural stem cells (NSCs) throughout the developing central nervous system is still unclear. In the Drosophila ventral nerve cord and central brain, asymmetrically dividing NSCs, called neuroblasts (NBs), progress through a series of sequentially expressed transcription factors that limits self-renewal by silencing a genetic module involving the transcription factor Chinmo. Here, we find that Chinmo also promotes neuroepithelium growth in the optic lobe during early larval stages by boosting symmetric self-renewing divisions while preventing differentiation. Neuroepithelium differentiation in late larvae requires the transcriptional silencing of chinmo by ecdysone, the main steroid hormone, therefore allowing coordination of neural stem cell self-renewal with organismal growth. In contrast, chinmo silencing in NBs is post-transcriptional and does not require ecdysone. Thus, during Drosophila development, humoral cues or tissue-intrinsic temporal specification programs respectively limit self-renewal in different types of neural progenitors through the transcriptional and post-transcriptional regulation of the same transcription factor. © 2018. Published by The Company of Biologists Ltd.

Neural prostheses in clinical applications--trends from precision mechanics towards biomedical microsystems in neurological rehabilitation.

PubMed

Stieglitz, T; Schuettler, M; Koch, K P

2004-04-01

Neural prostheses partially restore body functions by technical nerve excitation after trauma or neurological diseases. External devices and implants have been developed since the early 1960s for many applications. Several systems have reached nowadays clinical practice: Cochlea implants help the deaf to hear, micturition is induced by bladder stimulators in paralyzed persons and deep brain stimulation helps patients with Parkinson's disease to participate in daily life again. So far, clinical neural prostheses are fabricated with means of precision mechanics. Since microsystem technology opens the opportunity to design and develop complex systems with a high number of electrodes to interface with the nervous systems, the opportunity for selective stimulation and complex implant scenarios seems to be feasible in the near future. The potentials and limitations with regard to biomedical microdevices are introduced and discussed in this paper. Target specifications are derived from existing implants and are discussed on selected applications that has been investigated in experimental research: a micromachined implant to interface a nerve stump with a sieve electrode, cuff electrodes with integrated electronics, and an epiretinal vision prosthesis.

Transitions in sensitive period attachment learning in infancy: the role of corticosterone.

PubMed

Sullivan, Regina M; Holman, Parker J

2010-05-01

Survival of altricial infants, including humans and rats, depends on attachment to the caregiver - a process that requires infants to recognize, learn, and remember their attachment figure. The demands of a dynamic environment combined with a maturing organism require frequent neurobehavioral reorganization. This restructuring of behavior and its supporting neural circuitry can be viewed through the unique lens of attachment learning in rats in which preference learning is enhanced and aversion learning is attenuated. Behavioral restructuring is well adapted to securing the crucial infant-caregiver relationship regardless of the quality of care. With maturation and the end of the infant-caregiver attachment learning period, the complex interplay of neural structures, hormones, and social behavior coordinates the developing rat's eventual transition to life outside of the nest. Nevertheless, early-life environmental and physiological stressors can alter the resilient nature of this system, particularly with respect to the amygdala, and these changes may provide important clues to understanding the lasting effects of early stress. (c) 2009 Elsevier Ltd. All rights reserved.

Detection of Hypertension Retinopathy Using Deep Learning and Boltzmann Machines

NASA Astrophysics Data System (ADS)

Triwijoyo, B. K.; Pradipto, Y. D.

2017-01-01

hypertensive retinopathy (HR) in the retina of the eye is disturbance caused by high blood pressure disease, where there is a systemic change of arterial in the blood vessels of the retina. Most heart attacks occur in patients caused by high blood pressure symptoms of undiagnosed. Hypertensive retinopathy Symptoms such as arteriolar narrowing, retinal haemorrhage and cotton wool spots. Based on this reasons, the early diagnosis of the symptoms of hypertensive retinopathy is very urgent to aim the prevention and treatment more accurate. This research aims to develop a system for early detection of hypertension retinopathy stage. The proposed method is to determine the combined features artery and vein diameter ratio (AVR) as well as changes position with Optic Disk (OD) in retinal images to review the classification of hypertensive retinopathy using Deep Neural Networks (DNN) and Boltzmann Machines approach. We choose this approach of because based on previous research DNN models were more accurate in the image pattern recognition, whereas Boltzmann machines selected because It requires speedy iteration in the process of learning neural network. The expected results from this research are designed a prototype system early detection of hypertensive retinopathy stage and analysed the effectiveness and accuracy of the proposed methods.

Neural crest contribution to lingual mesenchyme, epithelium and developing taste papillae and taste buds.

PubMed

Liu, Hong-Xiang; Komatsu, Yoshihiro; Mishina, Yuji; Mistretta, Charlotte M

2012-08-15

The epithelium of mammalian tongue hosts most of the taste buds that transduce gustatory stimuli into neural signals. In the field of taste biology, taste bud cells have been described as arising from "local epithelium", in distinction from many other receptor organs that are derived from neurogenic ectoderm including neural crest (NC). In fact, contribution of NC to both epithelium and mesenchyme in the developing tongue is not fully understood. In the present study we used two independent, well-characterized mouse lines, Wnt1-Cre and P0-Cre that express Cre recombinase in a NC-specific manner, in combination with two Cre reporter mouse lines, R26R and ZEG, and demonstrate a contribution of NC-derived cells to both tongue mesenchyme and epithelium including taste papillae and taste buds. In tongue mesenchyme, distribution of NC-derived cells is in close association with taste papillae. In tongue epithelium, labeled cells are observed in an initial scattered distribution and progress to a clustered pattern between papillae, and within papillae and early taste buds. This provides evidence for a contribution of NC to lingual epithelium. Together with previous reports for the origin of taste bud cells from local epithelium in postnatal mouse, we propose that NC cells migrate into and reside in the epithelium of the tongue primordium at an early embryonic stage, acquire epithelial cell phenotypes, and undergo cell proliferation and differentiation that is involved in the development of taste papillae and taste buds. Our findings lead to a new concept about derivation of taste bud cells that include a NC origin. Copyright © 2012 Elsevier Inc. All rights reserved.

Development of Effective Connectivity during Own- and Other-Race Face Processing: A Granger Causality Analysis

PubMed Central

Zhou, Guifei; Liu, Jiangang; Ding, Xiao Pan; Fu, Genyue; Lee, Kang

2016-01-01

Numerous developmental studies have suggested that other-race effect (ORE) in face recognition emerges as early as in infancy and develops steadily throughout childhood. However, there is very limited research on the neural mechanisms underlying this developmental ORE. The present study used Granger causality analysis (GCA) to examine the development of children's cortical networks in processing own- and other-race faces. Children were between 3 and 13 years. An old-new paradigm was used to assess their own- and other-race face recognition with ETG-4000 (Hitachi Medical Co., Japan) acquiring functional near infrared spectroscopy (fNIRS) data. After preprocessing, for each participant and under each face condition, we obtained the causal map by calculating the weights of causal relations between the time courses of [oxy-Hb] of each pair of channels using GCA. To investigate further the differential causal connectivity for own-race faces and other-race faces at the group level, a repeated measure analysis of variance (ANOVA) was performed on the GCA weights for each pair of channels with the face race task (own-race face vs. other-race face) as the within-subject variable and the age as a between-subject factor (continuous variable). We found an age-related increase in functional connectivity, paralleling a similar age-related improvement in behavioral face processing ability. More importantly, we found that the significant differences in neural functional connectivity between the recognition of own-race faces and that of other-race faces were modulated by age. Thus, like the behavioral ORE, the neural ORE emerges early and undergoes a protracted developmental course. PMID:27713696

The cellular and molecular basis of cnidarian neurogenesis.

PubMed

Rentzsch, Fabian; Layden, Michael; Manuel, Michaël

2017-01-01

Neurogenesis initiates during early development and it continues through later developmental stages and in adult animals to enable expansion, remodeling, and homeostasis of the nervous system. The generation of nerve cells has been analyzed in detail in few bilaterian model organisms, leaving open many questions about the evolution of this process. As the sister group to bilaterians, cnidarians occupy an informative phylogenetic position to address the early evolution of cellular and molecular aspects of neurogenesis and to understand common principles of neural development. Here we review studies in several cnidarian model systems that have revealed significant similarities and interesting differences compared to neurogenesis in bilaterian species, and between different cnidarian taxa. Cnidarian neurogenesis is currently best understood in the sea anemone Nematostella vectensis, where it includes epithelial neural progenitor cells that express transcription factors of the soxB and atonal families. Notch signaling regulates the number of these neural progenitor cells, achaete-scute and dmrt genes are required for their further development and Wnt and BMP signaling appear to be involved in the patterning of the nervous system. In contrast to many vertebrates and Drosophila, cnidarians have a high capacity to generate neurons throughout their lifetime and during regeneration. Utilizing this feature of cnidarian biology will likely allow gaining new insights into the similarities and differences of embryonic and regenerative neurogenesis. The use of different cnidarian model systems and their expanding experimental toolkits will thus continue to provide a better understanding of evolutionary and developmental aspects of nervous system formation. WIREs Dev Biol 2017, 6:e257. doi: 10.1002/wdev.257 For further resources related to this article, please visit the WIREs website. © 2016 The Authors. WIREs Developmental Biology published by Wiley Periodicals, Inc.

Neural Correlates of Action Observation and Execution in 14-Month-Old Infants: An Event-Related EEG Desynchronization Study

ERIC Educational Resources Information Center

Marshall, Peter J.; Young, Thomas; Meltzoff, Andrew N.

2011-01-01

There is increasing interest in neurobiological methods for investigating the shared representation of action perception and production in early development. We explored the extent and regional specificity of EEG desynchronization in the infant alpha frequency range (6-9 Hz) during action observation and execution in 14-month-old infants.…

Planar induction of anteroposterior pattern in the developing central nervous system of Xenopus laevis

NASA Technical Reports Server (NTRS)

Doniach, T.; Phillips, C. R.; Gerhart, J. C.

1992-01-01

It has long been thought that anteroposterior (A-P) pattern in the vertebrate central nervous system is induced in the embryo's dorsal ectoderm exclusively by signals passing vertically from underlying, patterned dorsal mesoderm. Explants from early gastrulae of the frog Xenopus laevis were prepared in which vertical contact between dorsal ectoderm and mesoderm was prevented but planar contact was maintained. In these, four position-specific neural markers (engrailed-2, Krox-20, XlHbox 1, and XlHbox 6) were expressed in the ectoderm in the same A-P order as in the embryo. Thus, planar signals alone, following a path available in the normal embryo, can induce A-P neural pattern.

Flexing dual-systems models: How variable cognitive control in children informs our understanding of risk-taking across development.

PubMed

Li, Rosa

2017-10-01

Prevailing models of the development of decision-making propose that peak risk-taking occurs in adolescence due to a neural imbalance between two processes: gradual, linearly developing cognitive control and rapid, non-linearly developing reward-processing. Though many studies have found neural evidence supporting this dual-systems imbalance model, its behavioral predictions have been surprisingly difficult to document. Most laboratory studies have not found adolescents to exhibit greater risk-taking than children, and public health data show everyday risk-taking to peak in late adolescence/early adulthood. Moreover, when adolescents are provided detailed information about decision options and consequences, they evince similar behavior to adults. Such findings point to a critical feature of the development of decision-making that is missed by imbalance models. Specifically, the engagement of cognitive control is context dependent, such that cognitive control and therefore advantageous decision-making increases when available information is high and decreases when available information is low. Furthermore, the context dependence of cognitive control varies across development, such that increased information availability benefits children more than adolescents, who benefit more than adults. This review advances a flexible dual-systems model that is only imbalanced under certain conditions; explains disparities between neural, behavioral, and public health findings; and provides testable hypotheses for future research. Copyright © 2017 The Author. Published by Elsevier Ltd.. All rights reserved.

The Neural Border: Induction, Specification and Maturation of the territory that generates Neural Crest cells.

PubMed

Pla, Patrick; Monsoro-Burq, Anne H

2018-05-28

The neural crest is induced at the edge between the neural plate and the nonneural ectoderm, in an area called the neural (plate) border, during gastrulation and neurulation. In recent years, many studies have explored how this domain is patterned, and how the neural crest is induced within this territory, that also participates to the prospective dorsal neural tube, the dorsalmost nonneural ectoderm, as well as placode derivatives in the anterior area. This review highlights the tissue interactions, the cell-cell signaling and the molecular mechanisms involved in this dynamic spatiotemporal patterning, resulting in the induction of the premigratory neural crest. Collectively, these studies allow building a complex neural border and early neural crest gene regulatory network, mostly composed by transcriptional regulations but also, more recently, including novel signaling interactions. Copyright © 2018. Published by Elsevier Inc.

Genetic algorithm for neural networks optimization

NASA Astrophysics Data System (ADS)

Setyawati, Bina R.; Creese, Robert C.; Sahirman, Sidharta

2004-11-01

This paper examines the forecasting performance of multi-layer feed forward neural networks in modeling a particular foreign exchange rates, i.e. Japanese Yen/US Dollar. The effects of two learning methods, Back Propagation and Genetic Algorithm, in which the neural network topology and other parameters fixed, were investigated. The early results indicate that the application of this hybrid system seems to be well suited for the forecasting of foreign exchange rates. The Neural Networks and Genetic Algorithm were programmed using MATLAB«.

Early Language Learning and Literacy: Neuroscience Implications for Education

PubMed Central

Kuhl, Patricia K.

2011-01-01

The last decade has produced an explosion in neuroscience research examining young children’s early processing of language that has implications for education. Noninvasive, safe functional brain measurements have now been proven feasible for use with children starting at birth. In the arena of language, the neural signatures of learning can be documented at a remarkably early point in development, and these early measures predict performance in children’s language and pre-reading abilities in the second, third, and fifth year of life, a finding with theoretical and educational import. There is evidence that children’s early mastery of language requires learning in a social context, and this finding also has important implications for education. Evidence relating socio-economic status (SES) to brain function for language suggests that SES should be considered a proxy for the opportunity to learn and that the complexity of language input is a significant factor in developing brain areas related to language. The data indicate that the opportunity to learn from complex stimuli and events are vital early in life, and that success in school begins in infancy. PMID:21892359

Early Metamorphic Insertion Technology for Insect Flight Behavior Monitoring

PubMed Central

Bozkurt, Alper

2014-01-01

Early Metamorphosis Insertion Technology (EMIT) is a novel methodology for integrating microfabricated neuromuscular recording and actuation platforms on insects during their metamorphic development. Here, the implants are fused within the structure and function of the neuromuscular system as a result of metamorphic tissue remaking. The implants emerge with the insect where the development of tissue around the electronics during pupal development results in a bioelectrically and biomechanically enhanced tissue interface. This relatively more reliable and stable interface would be beneficial for many researchers exploring the neural basis of the insect locomotion with alleviated traumatic effects caused during adult stage insertions. In this article, we implant our electrodes into the indirect flight muscles of Manduca sexta. Located in the dorsal-thorax, these main flight powering dorsoventral and dorsolongitudinal muscles actuate the wings and supply the mechanical power for up and down strokes. Relative contraction of these two muscle groups has been under investigation to explore how the yaw maneuver is neurophysiologically coordinated. To characterize the flight dynamics, insects are often tethered with wires and their flight is recorded with digital cameras. We also developed a novel way to tether Manduca sexta on a magnetically levitating frame where the insect is connected to a commercially available wireless neural amplifier. This set up can be used to limit the degree of freedom to yawing “only” while transmitting the related electromyography signals from dorsoventral and dorsolongitudinal muscle groups. PMID:25079130

ZDHHC16 modulates FGF/ERK dependent proliferation of neural stem/progenitor cells in the zebrafish telencephalon.

PubMed

Shi, Wei; Chen, Xueran; Wang, Fen; Gao, Ming; Yang, Yang; Du, Zhaoxia; Wang, Chen; Yao, Yao; He, Kun; Hao, Aijun

2016-09-01

In vertebrates, neural stem/progenitor cells (NSPCs) maintenance is critical for nervous system development and homeostasis. However, the molecular mechanisms underlying the maintenance of NSPCs have not been fully elucidated. Here, we demonstrated that zebrafish ZDHHC16, a DHHC encoding protein, which was related to protein palmitoylation after translation, was expressed in the developing forebrain, and especially in the telencephalon. Loss- and gain-of-function studies showed that ZDHHC16 played a crucial role in the regualtion of NSPCs proliferation during zebrafish telencephalic development, via a mechanism dependent on its palmitoyltransferase activity. Further analyses showed that the inhibition of ZDHHC16 led to inactivation of the FGF/ERK signaling pathway during telencephalic NSPCs proliferation and maintenance. Taken together, our results suggest that ZDHHC16 activity is essential for early NSPCs proliferation where it acts to activate the FGF/ERK network, allowing for the initiation of proliferation -regulated gene expression programs. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1014-1028, 2016. © 2016 Wiley Periodicals, Inc.

Translational Neuroscience as a Tool for Intervention Development in the Context of High-Adversity Families

PubMed Central

Fisher, Philip A.

2017-01-01

The use of theory-driven models to develop and evaluate family-based intervention programs has a long history in psychology. Some of the first evidence-based parenting programs to address child problem behavior, developed in the 1970s, were grounded in causal models derived from longitudinal developmental research. The same translational strategies can also be applied to designing programs that leverage emerging scientific knowledge about the effects of early adverse experiences on neurobiological systems to reduce risk and promote well-being. By specifying not only behavioral targets but also affected underlying neural systems, interventions can become more precise and efficient. This chapter describes the development of a program of research focusing on an intervention for young children in foster care. The intervention emerged from social learning theory research and employs a translational neuroscience approach. The conceptual model guiding the research, which incorporates behavioral domains as well as stress-regulatory neural systems, is described. Finally, future directions for translational neuroscience in family-based intervention research are considered. PMID:27589501

Postnatal brain development: Structural imaging of dynamic neurodevelopmental processes

PubMed Central

Jernigan, Terry L.; Baaré, William F. C.; Stiles, Joan; Madsen, Kathrine Skak

2013-01-01

After birth, there is striking biological and functional development of the brain’s fiber tracts as well as remodeling of cortical and subcortical structures. Behavioral development in children involves a complex and dynamic set of genetically guided processes by which neural structures interact constantly with the environment. This is a protracted process, beginning in the third week of gestation and continuing into early adulthood. Reviewed here are studies using structural imaging techniques, with a special focus on diffusion weighted imaging, describing age-related brain maturational changes in children and adolescents, as well as studies that link these changes to behavioral differences. Finally, we discuss evidence for effects on the brain of several factors that may play a role in mediating these brain–behavior associations in children, including genetic variation, behavioral interventions, and hormonal variation associated with puberty. At present longitudinal studies are few, and we do not yet know how variability in individual trajectories of biological development in specific neural systems map onto similar variability in behavioral trajectories. PMID:21489384

School-Based Sex Education and Neuroscience: What We Know About Sex, Romance, Marriage, and Adolescent Brain Development.

PubMed

Ballonoff Suleiman, Ahna; Johnson, Megan; Shirtcliff, Elizabeth A; Galván, Adriana

2015-08-01

Many school-based abstinence-only sex education curricula state that sexual activity outside of marriage is likely to have harmful psychological effects. Recent advances in neuroscience have expanded our understanding of the neural underpinnings of romantic love, marriage, sexual desire, and sexual behavior and improved our understanding of adolescent brain development. In this article, we review recent advances in neuroscience and clarify what is known about the link between neural development and adolescent romantic and sexual behavior and what opportunities exist for future research. Whereas the evidence from neuroscience does not yet allow for clear conclusions about the cost or benefits of early romantic relationships and sexual behavior, it does indicate that providing developmentally appropriate education contributes to lifelong sexual health. Developing policies and practices for school-based sex education that reflect current research will best support the sexual and reproductive health of adolescents throughout their lives. © 2015, American School Health Association.

Dystrophic Serotonin Axons in Postmortem Brains from Young Autism Patients

PubMed Central

Azmitia, Efrain C.; Singh, Jorawer S.; Hou, Xiao P.; Wiegel, Jerzy

2014-01-01

Autism causes neuropathological changes in varied anatomical loci. A coherent neural mechanism to explain the spectrum of autistic symptomatology has not been proposed because most anatomical researchers focus on point-to-point functional neural systems (e.g. auditory, social networks) rather than considering global chemical neural systems. Serotonergic neurons have a global innervation pattern. Their cell bodies are found in the midbrain but they project their axons throughout the neural axis beginning in the fetal brain. This global system is implicated in autism by animal models and by biochemical, imaging, pharmacological, and genetics studies. However, no anatomical studies of the 5-HT innervation of autistic donors have been reported. Our review presents immunocytochemical evidence of an increase in 5-HT axons in post-mortem brain tissue from autism donors aged 2.8 to 29 years relative to controls. This increase is observed in the principle ascending fiber bundles of the medial and lateral forebrain bundles, and in the innervation density of the amygdala and the piriform, superior temporal, and parahippocampal cortices. In autistic donors eight years of age and up, several types of dystrophic 5-HT axons were seen in the termination fields. One class of these dystrophic axons, the thick heavily stained axons, was not seen in the brains of patients with neurodegenerative diseases. These findings provide morphological evidence for the involvement of serotonin neurons in the early etiology of autism, and suggest a diet therapy may be effective to blunt serotonin’s trophic actions during early brain development in children. PMID:21901837

Dystrophic serotonin axons in postmortem brains from young autism patients.

PubMed

Azmitia, Efrain C; Singh, Jorawer S; Hou, Xiao P; Wegiel, Jerzy

2011-10-01

Autism causes neuropathological changes in varied anatomical loci. A coherent neural mechanism to explain the spectrum of autistic symptomatology has not been proposed because most anatomical researchers focus on point-to-point functional neural systems (e.g., auditory and social networks) rather than considering global chemical neural systems. Serotonergic neurons have a global innervation pattern. Disorders Research Program, AS073234, Program Project (JW). Their cell bodies are found in the midbrain but they project their axons throughout the neural axis beginning in the fetal brain. This global system is implicated in autism by animal models and by biochemical, imaging, pharmacological, and genetics studies. However, no anatomical studies of the 5-HT innervation of autistic donors have been reported. Our review presents immunocytochemical evidence of an increase in 5-HT axons in postmortem brain tissue from autism donors aged 2.8-29 years relative to controls. This increase is observed in the principle ascending fiber bundles of the medial and lateral forebrain bundles, and in the innervation density of the amygdala and the piriform, superior temporal, and parahippocampal cortices. In autistic donors 8 years of age and up, several types of dystrophic 5-HT axons were seen in the termination fields. One class of these dystrophic axons, the thick heavily stained axons, was not seen in the brains of patients with neurodegenerative diseases. These findings provide morphological evidence for the involvement of serotonin neurons in the early etiology of autism, and suggest new therapies may be effective to blunt serotonin's trophic actions during early brain development in children. Copyright © 2011 Wiley-Liss, Inc.

Precursors to morality in development as a complex interplay between neural, socioenvironmental, and behavioral facets

PubMed Central

Cowell, Jason M.; Decety, Jean

2015-01-01

The nature and underpinnings of infants’ seemingly complex, third-party, social evaluations remain highly contentious. Theoretical perspectives oscillate between rich and lean interpretations of the same expressed preferences. Although some argue that infants and toddlers possess a “moral sense” based on core knowledge of the social world, others suggest that social evaluations are hierarchical in nature and the product of an integration of rudimentary general processes such as attention allocation and approach and avoidance. Moreover, these biologically prepared minds interact in social environments that include significant variation, which are likely to impact early social evaluations and behavior. The present study examined the neural underpinnings of and precursors to moral sensitivity in infants and toddlers (n = 73, ages 12–24 mo) through a series of interwoven measures, combining multiple levels of analysis including electrophysiological, eye-tracking, behavioral, and socioenvironmental. Continuous EEG and time-locked event-related potentials (ERPs) and gaze fixation were recorded while children watched characters engaging in prosocial and antisocial actions in two different tasks. All children demonstrated a neural differentiation in both spectral EEG power density modulations and time-locked ERPs when perceiving prosocial or antisocial agents. Time-locked neural differences predicted children’s preference for prosocial characters and were influenced by parental values regarding justice and fairness. Overall, this investigation casts light on the fundamental nature of moral cognition, including its underpinnings in general processes such as attention and approach–withdrawal, providing plausible mechanisms of early change and a foundation for forward movement in the field of developmental social neuroscience. PMID:26324885

mSEL-1L (Suppressor/Enhancer Lin12-like) Protein Levels Influence Murine Neural Stem Cell Self-renewal and Lineage Commitment*

PubMed Central

Cardano, Marina; Diaferia, Giuseppe R.; Cattaneo, Monica; Dessì, Sara S.; Long, Qiaoming; Conti, Luciano; DeBlasio, Pasquale; Cattaneo, Elena; Biunno, Ida

2011-01-01

Murine SEL-1L (mSEL-1L) is a key component of the endoplasmic reticulum-associated degradation pathway. It is essential during development as revealed by the multi-organ dysfunction and in uterus lethality occurring in homozygous mSEL-1L-deficient mice. Here we show that mSEL-1L is highly expressed in pluripotent embryonic stem cells and multipotent neural stem cells (NSCs) but silenced in all mature neural derivatives (i.e. astrocytes, oligodendrocytes, and neurons) by mmu-miR-183. NSCs derived from homozygous mSEL-1L-deficient embryos (mSEL-1L−/− NSCs) fail to proliferate in vitro, show a drastic reduction of the Notch effector HES-5, and reveal a significant down-modulation of the early neural progenitor markers PAX-6 and OLIG-2, when compared with the wild type (mSEL-1L+/+ NSCs) counterpart. Furthermore, these cells are almost completely deprived of the neural marker Nestin, display a significant decrease of SOX-2 expression, and rapidly undergo premature astrocytic commitment and apoptosis. The data suggest severe self-renewal defects occurring in these cells probably mediated by misregulation of the Notch signaling. The results reported here denote mSEL-1L as a primitive marker with a possible involvement in the regulation of neural progenitor stemness maintenance and lineage determination. PMID:21454627

mSEL-1L (Suppressor/enhancer Lin12-like) protein levels influence murine neural stem cell self-renewal and lineage commitment.

PubMed

Cardano, Marina; Diaferia, Giuseppe R; Cattaneo, Monica; Dessì, Sara S; Long, Qiaoming; Conti, Luciano; Deblasio, Pasquale; Cattaneo, Elena; Biunno, Ida

2011-05-27

Murine SEL-1L (mSEL-1L) is a key component of the endoplasmic reticulum-associated degradation pathway. It is essential during development as revealed by the multi-organ dysfunction and in uterus lethality occurring in homozygous mSEL-1L-deficient mice. Here we show that mSEL-1L is highly expressed in pluripotent embryonic stem cells and multipotent neural stem cells (NSCs) but silenced in all mature neural derivatives (i.e. astrocytes, oligodendrocytes, and neurons) by mmu-miR-183. NSCs derived from homozygous mSEL-1L-deficient embryos (mSEL-1L(-/-) NSCs) fail to proliferate in vitro, show a drastic reduction of the Notch effector HES-5, and reveal a significant down-modulation of the early neural progenitor markers PAX-6 and OLIG-2, when compared with the wild type (mSEL-1L(+/+) NSCs) counterpart. Furthermore, these cells are almost completely deprived of the neural marker Nestin, display a significant decrease of SOX-2 expression, and rapidly undergo premature astrocytic commitment and apoptosis. The data suggest severe self-renewal defects occurring in these cells probably mediated by misregulation of the Notch signaling. The results reported here denote mSEL-1L as a primitive marker with a possible involvement in the regulation of neural progenitor stemness maintenance and lineage determination.

The altered expression of perineuronal net elements during neural differentiation.

PubMed

Eskici, Nazli F; Erdem-Ozdamar, Sevim; Dayangac-Erden, Didem

2018-01-01

Perineuronal nets (PNNs), which are localized around neurons during development, are specialized forms of neural extracellular matrix with neuroprotective and plasticity-regulating roles. Hyaluronan and proteoglycan link protein 1 (HAPLN1), tenascin-R (TNR) and aggrecan (ACAN) are key elements of PNNs. In diseases characterized by neuritogenesis defects, the expression of these proteins is known to be downregulated, suggesting that PNNs may have a role in neural differentiation. In this study, the mRNA and protein levels of HAPLN1, TNR and ACAN were determined and compared at specific time points of neural differentiation. We used PC12 cells as the in vitro model because they reflect this developmental process. On day 7, the HAPLN1 mRNA level showed a 2.9-fold increase compared to the non-differentiated state. However, the cellular HAPLN1 protein level showed a decrease, indicating that the protein may have roles in neural differentiation, and may be secreted during the early period of differentiation. By contrast, TNR mRNA and protein levels remained unchanged, and the amount of cellular ACAN protein showed a 3.7-fold increase at day 7. These results suggest that ACAN may be secreted after day 7, possibly due to its large amount of post-translational modifications. Our results provide preliminary data on the expression of PNN elements during neural differentiation. Further investigations will be performed on the role of these elements in neurological disease models.

Neural Language Processing in Adolescent First-Language Learners: Longitudinal Case Studies in American Sign Language.

PubMed

Ferjan Ramirez, Naja; Leonard, Matthew K; Davenport, Tristan S; Torres, Christina; Halgren, Eric; Mayberry, Rachel I

2016-03-01

One key question in neurolinguistics is the extent to which the neural processing system for language requires linguistic experience during early life to develop fully. We conducted a longitudinal anatomically constrained magnetoencephalography (aMEG) analysis of lexico-semantic processing in 2 deaf adolescents who had no sustained language input until 14 years of age, when they became fully immersed in American Sign Language. After 2 to 3 years of language, the adolescents' neural responses to signed words were highly atypical, localizing mainly to right dorsal frontoparietal regions and often responding more strongly to semantically primed words (Ferjan Ramirez N, Leonard MK, Torres C, Hatrak M, Halgren E, Mayberry RI. 2014. Neural language processing in adolescent first-language learners. Cereb Cortex. 24 (10): 2772-2783). Here, we show that after an additional 15 months of language experience, the adolescents' neural responses remained atypical in terms of polarity. While their responses to less familiar signed words still showed atypical localization patterns, the localization of responses to highly familiar signed words became more concentrated in the left perisylvian language network. Our findings suggest that the timing of language experience affects the organization of neural language processing; however, even in adolescence, language representation in the human brain continues to evolve with experience. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Neural Networks for Modeling and Control of Particle Accelerators

DOE Office of Scientific and Technical Information (OSTI.GOV)

Edelen, A. L.; Biedron, S. G.; Chase, B. E.

Myriad nonlinear and complex physical phenomena are host to particle accelerators. They often involve a multitude of interacting systems, are subject to tight performance demands, and should be able to run for extended periods of time with minimal interruptions. Often times, traditional control techniques cannot fully meet these requirements. One promising avenue is to introduce machine learning and sophisticated control techniques inspired by artificial intelligence, particularly in light of recent theoretical and practical advances in these fields. Within machine learning and artificial intelligence, neural networks are particularly well-suited to modeling, control, and diagnostic analysis of complex, nonlinear, and time-varying systems,more » as well as systems with large parameter spaces. Consequently, the use of neural network-based modeling and control techniques could be of significant benefit to particle accelerators. For the same reasons, particle accelerators are also ideal test-beds for these techniques. Moreover, many early attempts to apply neural networks to particle accelerators yielded mixed results due to the relative immaturity of the technology for such tasks. For the purpose of this paper is to re-introduce neural networks to the particle accelerator community and report on some work in neural network control that is being conducted as part of a dedicated collaboration between Fermilab and Colorado State University (CSU). We also describe some of the challenges of particle accelerator control, highlight recent advances in neural network techniques, discuss some promising avenues for incorporating neural networks into particle accelerator control systems, and describe a neural network-based control system that is being developed for resonance control of an RF electron gun at the Fermilab Accelerator Science and Technology (FAST) facility, including initial experimental results from a benchmark controller.« less

Neural Networks for Modeling and Control of Particle Accelerators

NASA Astrophysics Data System (ADS)

Edelen, A. L.; Biedron, S. G.; Chase, B. E.; Edstrom, D.; Milton, S. V.; Stabile, P.

2016-04-01

Particle accelerators are host to myriad nonlinear and complex physical phenomena. They often involve a multitude of interacting systems, are subject to tight performance demands, and should be able to run for extended periods of time with minimal interruptions. Often times, traditional control techniques cannot fully meet these requirements. One promising avenue is to introduce machine learning and sophisticated control techniques inspired by artificial intelligence, particularly in light of recent theoretical and practical advances in these fields. Within machine learning and artificial intelligence, neural networks are particularly well-suited to modeling, control, and diagnostic analysis of complex, nonlinear, and time-varying systems, as well as systems with large parameter spaces. Consequently, the use of neural network-based modeling and control techniques could be of significant benefit to particle accelerators. For the same reasons, particle accelerators are also ideal test-beds for these techniques. Many early attempts to apply neural networks to particle accelerators yielded mixed results due to the relative immaturity of the technology for such tasks. The purpose of this paper is to re-introduce neural networks to the particle accelerator community and report on some work in neural network control that is being conducted as part of a dedicated collaboration between Fermilab and Colorado State University (CSU). We describe some of the challenges of particle accelerator control, highlight recent advances in neural network techniques, discuss some promising avenues for incorporating neural networks into particle accelerator control systems, and describe a neural network-based control system that is being developed for resonance control of an RF electron gun at the Fermilab Accelerator Science and Technology (FAST) facility, including initial experimental results from a benchmark controller.

Neural Networks for Modeling and Control of Particle Accelerators

DOE PAGES

Edelen, A. L.; Biedron, S. G.; Chase, B. E.; ...

2016-04-01

Myriad nonlinear and complex physical phenomena are host to particle accelerators. They often involve a multitude of interacting systems, are subject to tight performance demands, and should be able to run for extended periods of time with minimal interruptions. Often times, traditional control techniques cannot fully meet these requirements. One promising avenue is to introduce machine learning and sophisticated control techniques inspired by artificial intelligence, particularly in light of recent theoretical and practical advances in these fields. Within machine learning and artificial intelligence, neural networks are particularly well-suited to modeling, control, and diagnostic analysis of complex, nonlinear, and time-varying systems,more » as well as systems with large parameter spaces. Consequently, the use of neural network-based modeling and control techniques could be of significant benefit to particle accelerators. For the same reasons, particle accelerators are also ideal test-beds for these techniques. Moreover, many early attempts to apply neural networks to particle accelerators yielded mixed results due to the relative immaturity of the technology for such tasks. For the purpose of this paper is to re-introduce neural networks to the particle accelerator community and report on some work in neural network control that is being conducted as part of a dedicated collaboration between Fermilab and Colorado State University (CSU). We also describe some of the challenges of particle accelerator control, highlight recent advances in neural network techniques, discuss some promising avenues for incorporating neural networks into particle accelerator control systems, and describe a neural network-based control system that is being developed for resonance control of an RF electron gun at the Fermilab Accelerator Science and Technology (FAST) facility, including initial experimental results from a benchmark controller.« less

E-nose based rapid prediction of early mouldy grain using probabilistic neural networks

PubMed Central

Ying, Xiaoguo; Liu, Wei; Hui, Guohua; Fu, Jun

2015-01-01

In this paper, early mouldy grain rapid prediction method using probabilistic neural network (PNN) and electronic nose (e-nose) was studied. E-nose responses to rice, red bean, and oat samples with different qualities were measured and recorded. E-nose data was analyzed using principal component analysis (PCA), back propagation (BP) network, and PNN, respectively. Results indicated that PCA and BP network could not clearly discriminate grain samples with different mouldy status and showed poor predicting accuracy. PNN showed satisfying discriminating abilities to grain samples with an accuracy of 93.75%. E-nose combined with PNN is effective for early mouldy grain prediction. PMID:25714125

The roof plate boundary is a bi-directional organiser of dorsal neural tube and choroid plexus development

PubMed Central

Broom, Emma R.; Gilthorpe, Jonathan D.; Butts, Thomas; Campo-Paysaa, Florent; Wingate, Richard J. T.

2012-01-01

The roof plate is a signalling centre positioned at the dorsal midline of the central nervous system and generates dorsalising morphogenic signals along the length of the neuraxis. Within cranial ventricles, the roof plate gives rise to choroid plexus, which regulates the internal environment of the developing and adult brain and spinal cord via the secretion of cerebrospinal fluid. Using the fourth ventricle as our model, we show that the organiser properties of the roof plate are determined by its boundaries with the adjacent neuroepithelium. Through a combination of in ovo transplantation, co-culture and electroporation techniques in chick embryos between embryonic days 3 and 6, we demonstrate that organiser properties are maintained by interactions between the non-neural roof plate and the neural rhombic lip. At the molecular level, this interaction is mediated by Delta-Notch signalling and upregulation of the chick homologue of Hes1: chairy2. Gain- and loss-of-function approaches reveal that cdelta1 is both necessary and sufficient for organiser function. Our results also demonstrate that while chairy2 is specifically required for the maintenance of the organiser, its ectopic expression is not sufficient to recapitulate organiser properties. Expression of atonal1 in the rhombic lip adjacent at the roof plate boundary is acutely dependent on both boundary cell interactions and Delta-Notch signalling. Correspondingly, the roof plate boundary organiser also signals to the roof plate itself to specify the expression of early choroid plexus markers. Thus, the roof plate boundary organiser signals bi-directionally to acutely coordinate the development of adjacent neural and non-neural tissues. PMID:23052907

The roof plate boundary is a bi-directional organiser of dorsal neural tube and choroid plexus development.

PubMed

Broom, Emma R; Gilthorpe, Jonathan D; Butts, Thomas; Campo-Paysaa, Florent; Wingate, Richard J T

2012-11-01

The roof plate is a signalling centre positioned at the dorsal midline of the central nervous system and generates dorsalising morphogenic signals along the length of the neuraxis. Within cranial ventricles, the roof plate gives rise to choroid plexus, which regulates the internal environment of the developing and adult brain and spinal cord via the secretion of cerebrospinal fluid. Using the fourth ventricle as our model, we show that the organiser properties of the roof plate are determined by its boundaries with the adjacent neuroepithelium. Through a combination of in ovo transplantation, co-culture and electroporation techniques in chick embryos between embryonic days 3 and 6, we demonstrate that organiser properties are maintained by interactions between the non-neural roof plate and the neural rhombic lip. At the molecular level, this interaction is mediated by Delta-Notch signalling and upregulation of the chick homologue of Hes1: chairy2. Gain- and loss-of-function approaches reveal that cdelta1 is both necessary and sufficient for organiser function. Our results also demonstrate that while chairy2 is specifically required for the maintenance of the organiser, its ectopic expression is not sufficient to recapitulate organiser properties. Expression of atonal1 in the rhombic lip adjacent at the roof plate boundary is acutely dependent on both boundary cell interactions and Delta-Notch signalling. Correspondingly, the roof plate boundary organiser also signals to the roof plate itself to specify the expression of early choroid plexus markers. Thus, the roof plate boundary organiser signals bi-directionally to acutely coordinate the development of adjacent neural and non-neural tissues.

Brominated and organophosphate flame retardants target different neurodevelopmental stages, characterized with embryonic neural stem cells and neuronotypic PC12 cells.

PubMed

Slotkin, Theodore A; Skavicus, Samantha; Stapleton, Heather M; Seidler, Frederic J

2017-09-01

In addition to their activity as endocrine disruptors, brominated and organophosphate flame retardants are suspected to be developmental neurotoxicants, although identifying their specific mechanisms for that activity has been elusive. In the current study, we evaluated the effects of several flame retardants on neurodifferentiation using two in vitro models that assess distinct "decision nodes" in neural cell development: embryonic rat neural stem cells (NSCs), which evaluate the origination of neurons and glia from precursors, and rat neuronotypic PC12 cells, which characterize a later stage where cells committed to a neuronal phenotype undergo neurite outgrowth and neurotransmitter specification. In NSCs, both brominated and organophosphate flame retardants diverted the phenotype in favor of glia and away from formation of neurons, leading to an increased glia/neuron ratio, a common hallmark of the in vivo effects of neurotoxicants. For this early decision node, the brominated flame retardants were far more potent than the organophosphates. In PC12 cells, the brominated flame retardants were far less effective, whereas tris (1,3-dichloro-2-propyl) phosphate, an organophosphate, was more effective. Thus, the two classes of flame retardants differentially impact the two distinct vulnerable periods of neurodifferentiation. Furthermore, the effects on neurodifferentiation were separable from outright cytotoxicity, an important requirement in establishing a specific effect of these agents on neural cell development. These results reinforce the likelihood that flame retardants act as developmental neurotoxicants via direct effects on neural cell differentiation, over and above other activities that can impact nervous system development, such as endocrine disruption. Copyright © 2017 Elsevier B.V. All rights reserved.

Peak alpha frequency is a neural marker of cognitive function across the autism spectrum.

PubMed

Dickinson, Abigail; DiStefano, Charlotte; Senturk, Damla; Jeste, Shafali Spurling

2018-03-01

Cognitive function varies substantially and serves as a key predictor of outcome and response to intervention in autism spectrum disorder (ASD), yet we know little about the neurobiological mechanisms that underlie cognitive function in children with ASD. The dynamics of neuronal oscillations in the alpha range (6-12 Hz) are associated with cognition in typical development. Peak alpha frequency is also highly sensitive to developmental changes in neural networks, which underlie cognitive function, and therefore, it holds promise as a developmentally sensitive neural marker of cognitive function in ASD. Here, we measured peak alpha band frequency under a task-free condition in a heterogeneous sample of children with ASD (N = 59) and age-matched typically developing (TD) children (N = 38). At a group level, peak alpha frequency was decreased in ASD compared to TD children. Moreover, within the ASD group, peak alpha frequency correlated strongly with non-verbal cognition. As peak alpha frequency reflects the integrity of neural networks, our results suggest that deviations in network development may underlie cognitive function in individuals with ASD. By shedding light on the neurobiological correlates of cognitive function in ASD, our findings lay the groundwork for considering peak alpha frequency as a useful biomarker of cognitive function within this population which, in turn, will facilitate investigations of early markers of cognitive impairment and predictors of outcome in high risk infants. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Self-Disturbances as a Possible Premorbid Indicator of Schizophrenia Risk: A Neurodevelopmental Perspective

PubMed Central

Brent, Benjamin K.; Seidman, Larry J.; Thermenos, Heidi W.; Holt, Daphne J.; Keshavan, Matcheri S.

2013-01-01

Self-disturbances (SDs) are increasingly identified in schizophrenia and are theorized to confer vulnerability to psychosis. Neuroimaging research has shed some light on the neural correlates of SDs in schizophrenia. But, the onset and trajectory of the neural alterations underlying SDs in schizophrenia remain incompletely understood. We hypothesize that the aberrant structure and function of brain areas (e.g., prefrontal, lateral temporal, and parietal cortical structures) comprising the “neural circuitry of self” may represent an early, premorbid (i.e., pre-prodromal) indicator of schizophrenia risk. Consistent with neurodevelopmental models, we argue that “early” (i.e., perinatal) dysmaturational processes (e.g., abnormal cortical neural cell migration and mini-columnar formation) affecting key prefrontal (e.g., medial prefrontal cortex), lateral temporal cortical (e.g., superior temporal sulcus), parietal (e.g., inferior parietal lobule) structures involved in self-processing may lead to subtle disruptions of “self” during childhood in persons at risk for schizophrenia. During adolescence, progressive neurodevelopmental alterations (e.g., aberrant synaptic pruning) affecting the neural circuitry of self may contribute to worsening of SDs. This could result in the emergence of prodromal symptoms and, eventually, full-blown psychosis. To highlight why adolescence may be a period of heightened risk for SDs, we first summarize the literature regarding the neural correlates of self in typically developing children. Next, we present evidence from neuroimaging studies in genetic high-risk youth suggesting that fronto-temporal-parietal structures mediating self-reflection may be abnormal in the premorbid period. Our goal is that the ideas presented here might provide future directions for research into the neurobiology of SDs during the pre-psychosis development of youth at risk for schizophrenia. PMID:23932148

The microbiota-gut-brain axis as a key regulator of neural function and the stress response: Implications for human and animal health.

PubMed

Wiley, N C; Dinan, T G; Ross, R P; Stanton, C; Clarke, G; Cryan, J F

2017-07-01

The brain-gut-microbiota axis comprises an extensive communication network between the brain, the gut, and the microbiota residing there. Development of a diverse gut microbiota is vital for multiple features of behavior and physiology, as well as many fundamental aspects of brain structure and function. Appropriate early-life assembly of the gut microbiota is also believed to play a role in subsequent emotional and cognitive development. If the composition, diversity, or assembly of the gut microbiota is impaired, this impairment can have a negative impact on host health and lead to disorders such as obesity, diabetes, inflammatory diseases, and even potentially neuropsychiatric illnesses, including anxiety and depression. Therefore, much research effort in recent years has focused on understanding the potential of targeting the intestinal microbiota to prevent and treat such disorders. This review aims to explore the influence of the gut microbiota on host neural function and behavior, particularly those of relevance to stress-related disorders. The involvement of microbiota in diverse neural functions such as myelination, microglia function, neuronal morphology, and blood-brain barrier integrity across the life span, from early life to adolescence to old age, will also be discussed. Nurturing an optimal gut microbiome may also prove beneficial in animal science as a means to manage stressful situations and to increase productivity of farm animals. The implications of these observations are manifold, and researchers are hopeful that this promising body of preclinical work can be successfully translated to the clinic and beyond.

Impaired activity-dependent neural circuit assembly and refinement in autism spectrum disorder genetic models

PubMed Central

Doll, Caleb A.; Broadie, Kendal

2014-01-01

Early-use activity during circuit-specific critical periods refines brain circuitry by the coupled processes of eliminating inappropriate synapses and strengthening maintained synapses. We theorize these activity-dependent (A-D) developmental processes are specifically impaired in autism spectrum disorders (ASDs). ASD genetic models in both mouse and Drosophila have pioneered our insights into normal A-D neural circuit assembly and consolidation, and how these developmental mechanisms go awry in specific genetic conditions. The monogenic fragile X syndrome (FXS), a common cause of heritable ASD and intellectual disability, has been particularly well linked to defects in A-D critical period processes. The fragile X mental retardation protein (FMRP) is positively activity-regulated in expression and function, in turn regulates excitability and activity in a negative feedback loop, and appears to be required for the A-D remodeling of synaptic connectivity during early-use critical periods. The Drosophila FXS model has been shown to functionally conserve the roles of human FMRP in synaptogenesis, and has been centrally important in generating our current mechanistic understanding of the FXS disease state. Recent advances in Drosophila optogenetics, transgenic calcium reporters, highly-targeted transgenic drivers for individually-identified neurons, and a vastly improved connectome of the brain are now being combined to provide unparalleled opportunities to both manipulate and monitor A-D processes during critical period brain development in defined neural circuits. The field is now poised to exploit this new Drosophila transgenic toolbox for the systematic dissection of A-D mechanisms in normal versus ASD brain development, particularly utilizing the well-established Drosophila FXS disease model. PMID:24570656

Neurodevelopmental consequences of pediatric cancer and its treatment: applying an early adversity framework to understanding cognitive, behavioral, and emotional outcomes.

PubMed

Marusak, Hilary A; Iadipaolo, Allesandra S; Harper, Felicity W; Elrahal, Farrah; Taub, Jeffrey W; Goldberg, Elimelech; Rabinak, Christine A

2018-06-01

Today, children are surviving pediatric cancer at unprecedented rates, making it one of modern medicine's true success stories. However, we are increasingly becoming aware of several deleterious effects of cancer and the subsequent "cure" that extend beyond physical sequelae. Indeed, survivors of childhood cancer commonly report cognitive, emotional, and psychological difficulties, including attentional difficulties, anxiety, and posttraumatic stress symptoms (PTSS). Cognitive late- and long-term effects have been largely attributed to neurotoxic effects of cancer treatments (e.g., chemotherapy, cranial irradiation, surgery) on brain development. The role of childhood adversity in pediatric cancer - namely, the presence of a life-threatening disease and endurance of invasive medical procedures - has been largely ignored in the existing neuroscientific literature, despite compelling research by our group and others showing that exposure to more commonly studied adverse childhood experiences (i.e., domestic and community violence, physical, sexual, and emotional abuse) strongly imprints on neural development. While these adverse childhood experiences are different in many ways from the experience of childhood cancer (e.g., context, nature, source), they do share a common element of exposure to threat (i.e., threat to life or physical integrity). Therefore, we argue that the double hit of early threat and cancer treatments likely alters neural development, and ultimately, cognitive, behavioral, and emotional outcomes. In this paper, we (1) review the existing neuroimaging research on child, adolescent, and adult survivors of childhood cancer, (2) summarize gaps in our current understanding, (3) propose a novel neurobiological framework that characterizes childhood cancer as a type of childhood adversity, particularly a form of early threat, focusing on development of the hippocampus and the salience and emotion network (SEN), and (4) outline future directions for research.

Moderate alcohol exposure during early brain development increases stimulus-response habits in adulthood.

PubMed

Parker, Matthew O; Evans, Alexandra M-D; Brock, Alistair J; Combe, Fraser J; Teh, Muy-Teck; Brennan, Caroline H

2016-01-01

Exposure to alcohol during early central nervous system development has been shown variously to affect aspects of physiological and behavioural development. In extreme cases, this can extend to craniofacial defects, severe developmental delay and mental retardation. At more moderate levels, subtle differences in brain morphology and behaviour have been observed. One clear effect of developmental alcohol exposure is an increase in the propensity to develop alcoholism and other addictions. The mechanisms by which this occurs, however, are not currently understood. In this study, we tested the hypothesis that adult zebrafish chronically exposed to moderate levels of ethanol during early brain ontogenesis would show an increase in conditioned place preference for alcohol and an increased propensity towards habit formation, a key component of drug addiction in humans. We found support for both of these hypotheses and found that the exposed fish had changes in mRNA expression patterns for dopamine receptor, nicotinic acetylcholine receptor and μ-opioid receptor encoding genes. Collectively, these data show an explicit link between the increased proclivity for addiction and addiction-related behaviour following exposure to ethanol during early brain development and alterations in the neural circuits underlying habit learning. © 2014 Society for the Study of Addiction.

CRISPR/Cas9-mediated heterozygous knockout of the autism gene CHD8 and characterization of its transcriptional networks in neurodevelopment.

PubMed

Wang, Ping; Lin, Mingyan; Pedrosa, Erika; Hrabovsky, Anastasia; Zhang, Zheng; Guo, Wenjun; Lachman, Herbert M; Zheng, Deyou

2015-01-01

Disruptive mutation in the CHD8 gene is one of the top genetic risk factors in autism spectrum disorders (ASDs). Previous analyses of genome-wide CHD8 occupancy and reduced expression of CHD8 by shRNA knockdown in committed neural cells showed that CHD8 regulates multiple cell processes critical for neural functions, and its targets are enriched with ASD-associated genes. To further understand the molecular links between CHD8 functions and ASD, we have applied the CRISPR/Cas9 technology to knockout one copy of CHD8 in induced pluripotent stem cells (iPSCs) to better mimic the loss-of-function status that would exist in the developing human embryo prior to neuronal differentiation. We then carried out transcriptomic and bioinformatic analyses of neural progenitors and neurons derived from the CHD8 mutant iPSCs. Transcriptome profiling revealed that CHD8 hemizygosity (CHD8 (+/-)) affected the expression of several thousands of genes in neural progenitors and early differentiating neurons. The differentially expressed genes were enriched for functions of neural development, β-catenin/Wnt signaling, extracellular matrix, and skeletal system development. They also exhibited significant overlap with genes previously associated with autism and schizophrenia, as well as the downstream transcriptional targets of multiple genes implicated in autism. Providing important insight into how CHD8 mutations might give rise to macrocephaly, we found that seven of the twelve genes associated with human brain volume or head size by genome-wide association studies (e.g., HGMA2) were dysregulated in CHD8 (+/-) neural progenitors or neurons. We have established a renewable source of CHD8 (+/-) iPSC lines that would be valuable for investigating the molecular and cellular functions of CHD8. Transcriptomic profiling showed that CHD8 regulates multiple genes implicated in ASD pathogenesis and genes associated with brain volume.

The development of functional network organization in early childhood and early adolescence: A resting-state fNIRS study.

PubMed

Cai, Lin; Dong, Qi; Niu, Haijing

2018-04-01

Early childhood (7-8 years old) and early adolescence (11-12 years old) constitute two landmark developmental stages that comprise considerable changes in neural cognition. However, very limited information from functional neuroimaging studies exists on the functional topological configuration of the human brain during specific developmental periods. In the present study, we utilized continuous resting-state functional near-infrared spectroscopy (rs-fNIRS) imaging data to examine topological changes in network organization during development from early childhood and early adolescence to adulthood. Our results showed that the properties of small-worldness and modularity were not significantly different across development, demonstrating the developmental maturity of important functional brain organization in early childhood. Intriguingly, young children had a significantly lower global efficiency than early adolescents and adults, which revealed that the integration of the distributed networks strengthens across the developmental stages underlying cognitive development. Moreover, local efficiency of young children and adolescents was significantly lower than that of adults, while there was no difference between these two younger groups. This finding demonstrated that functional segregation remained relatively steady from early childhood to early adolescence, and the brain in these developmental periods possesses no optimal network configuration. Furthermore, we found heterogeneous developmental patterns in the regional nodal properties in various brain regions, such as linear increased nodal properties in the frontal cortex, indicating increasing cognitive capacity over development. Collectively, our results demonstrated that significant topological changes in functional network organization occurred during these two critical developmental stages, and provided a novel insight into elucidating subtle changes in brain functional networks across development. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Neural Correlates of Math Gains Vary Depending on Parental Socioeconomic Status (SES)

PubMed Central

Demir-Lira, Özlem Ece; Prado, Jérôme; Booth, James R.

2016-01-01

We used functional magnetic resonance imaging (fMRI) to examine the neural predictors of math development, and asked whether these predictors vary as a function of parental socioeconomic status (SES) in children ranging in age from 8 to 13 years. We independently localized brain regions subserving verbal versus spatial processing in order to characterize relations between activation in these regions during an arithmetic task and long-term change in math skill (up to 3 years). Neural predictors of math gains encompassed brain regions subserving both verbal and spatial processing, but the relation between relative reliance on these regions and math skill growth varied depending on parental SES. Activity in an area of the left inferior frontal gyrus (IFG) identified by the verbal localizer was related to greater growth in math skill at the higher end of the SES continuum, but lesser improvements at the lower end. Activity in an area of the right superior parietal cortex identified by the spatial localizer was related to greater growth in math skill at the lower end of the SES continuum, but lesser improvements at the higher end. Results highlight early neural mechanisms as possible neuromarkers of long-term arithmetic learning and suggest that neural predictors of math gains vary with parental SES. PMID:27378987

Tissue specific roles for the ribosome biogenesis factor Wdr43 in zebrafish development.

PubMed

Zhao, Chengtian; Andreeva, Viktoria; Gibert, Yann; LaBonty, Melissa; Lattanzi, Victoria; Prabhudesai, Shubhangi; Zhou, Yi; Zon, Leonard; McCann, Kathleen L; Baserga, Susan; Yelick, Pamela C

2014-01-01

During vertebrate craniofacial development, neural crest cells (NCCs) contribute to most of the craniofacial pharyngeal skeleton. Defects in NCC specification, migration and differentiation resulting in malformations in the craniofacial complex are associated with human craniofacial disorders including Treacher-Collins Syndrome, caused by mutations in TCOF1. It has been hypothesized that perturbed ribosome biogenesis and resulting p53 mediated neuroepithelial apoptosis results in NCC hypoplasia in mouse Tcof1 mutants. However, the underlying mechanisms linking ribosome biogenesis and NCC development remain poorly understood. Here we report a new zebrafish mutant, fantome (fan), which harbors a point mutation and predicted premature stop codon in zebrafish wdr43, the ortholog to yeast UTP5. Although wdr43 mRNA is widely expressed during early zebrafish development, and its deficiency triggers early neural, eye, heart and pharyngeal arch defects, later defects appear fairly restricted to NCC derived craniofacial cartilages. Here we show that the C-terminus of Wdr43, which is absent in fan mutant protein, is both necessary and sufficient to mediate its nucleolar localization and protein interactions in metazoans. We demonstrate that Wdr43 functions in ribosome biogenesis, and that defects observed in fan mutants are mediated by a p53 dependent pathway. Finally, we show that proper localization of a variety of nucleolar proteins, including TCOF1, is dependent on that of WDR43. Together, our findings provide new insight into roles for Wdr43 in development, ribosome biogenesis, and also ribosomopathy-induced craniofacial phenotypes including Treacher-Collins Syndrome.

An Initial Investigation of the Neural Correlates of Word Processing in Preschoolers With Specific Language Impairment.

PubMed

Haebig, Eileen; Leonard, Laurence; Usler, Evan; Deevy, Patricia; Weber, Christine

2018-03-15

Previous behavioral studies have found deficits in lexical-semantic abilities in children with specific language impairment (SLI), including reduced depth and breadth of word knowledge. This study explored the neural correlates of early emerging familiar word processing in preschoolers with SLI and typical development. Fifteen preschoolers with typical development and 15 preschoolers with SLI were presented with pictures followed after a brief delay by an auditory label that did or did not match. Event-related brain potentials were time locked to the onset of the auditory labels. Children provided verbal judgments of whether the label matched the picture. There were no group differences in the accuracy of identifying when pictures and labels matched or mismatched. Event-related brain potential data revealed that mismatch trials elicited a robust N400 in both groups, with no group differences in mean amplitude or peak latency. However, the typically developing group demonstrated a more robust late positive component, elicited by mismatch trials. These initial findings indicate that lexical-semantic access of early acquired words, indexed by the N400, does not differ between preschoolers with SLI and typical development when highly familiar words are presented in isolation. However, the typically developing group demonstrated a more mature profile of postlexical reanalysis and integration, indexed by an emerging late positive component. The findings lay the necessary groundwork for better understanding processing of newly learned words in children with SLI.

The Impact of Ecological Niche on Adaptive Flexibility of Sensory Circuitry

PubMed Central

Pallas, Sarah L.

2017-01-01

Evolution and development are interdependent, particularly with regard to the construction of the nervous system and its position as the machine that produces behavior. On the one hand, the processes directing development and plasticity of the brain provide avenues through which natural selection can sculpt neural cell fate and connectivity, and on the other hand, they are themselves subject to selection pressure. For example, mutations that produce heritable perturbations in neuronal birth and death rates, transcription factor expression, or availability of axon guidance factors within sensory pathways can markedly affect the development of form and thus the function of stimulus decoding circuitry. This evolvability of flexible circuits makes them more adaptable to environmental variation. Although there is general agreement on this point, whether the sensitivity of circuits to environmental influence and the mechanisms underlying development and plasticity of sensory pathways are similar across species from different ecological niches has received almost no attention. Neural circuits are generally more sensitive to environmental influences during an early critical period, but not all niches afford the same access to stimuli in early life. Furthermore, depending on predictability of the habitat and ecological niche, sensory coding circuits might be more susceptible to sensory experience in some species than in others. Despite decades of work on understanding the mechanisms underlying critical period plasticity, the importance of ecological niche in visual pathway development has received little attention. Here, I will explore the relationship between critical period plasticity and ecological niche in mammalian sensory pathways. PMID:28701910

The Impact of Ecological Niche on Adaptive Flexibility of Sensory Circuitry.

PubMed

Pallas, Sarah L

2017-01-01

Evolution and development are interdependent, particularly with regard to the construction of the nervous system and its position as the machine that produces behavior. On the one hand, the processes directing development and plasticity of the brain provide avenues through which natural selection can sculpt neural cell fate and connectivity, and on the other hand, they are themselves subject to selection pressure. For example, mutations that produce heritable perturbations in neuronal birth and death rates, transcription factor expression, or availability of axon guidance factors within sensory pathways can markedly affect the development of form and thus the function of stimulus decoding circuitry. This evolvability of flexible circuits makes them more adaptable to environmental variation. Although there is general agreement on this point, whether the sensitivity of circuits to environmental influence and the mechanisms underlying development and plasticity of sensory pathways are similar across species from different ecological niches has received almost no attention. Neural circuits are generally more sensitive to environmental influences during an early critical period, but not all niches afford the same access to stimuli in early life. Furthermore, depending on predictability of the habitat and ecological niche, sensory coding circuits might be more susceptible to sensory experience in some species than in others. Despite decades of work on understanding the mechanisms underlying critical period plasticity, the importance of ecological niche in visual pathway development has received little attention. Here, I will explore the relationship between critical period plasticity and ecological niche in mammalian sensory pathways.

The Impact of Early and Late Damage to the Human Amygdala on "Theory of Mind" Reasoning

ERIC Educational Resources Information Center

Shaw, P.; Lawrence, E. J.; Radbourne, C.; Bramham, J.; Polkey, C. E.; David, A. S.

2004-01-01

There is a burgeoning interest in the neural basis of the ability to attribute mental states to others; a capacity referred to as "theory of mind" (ToM). We examined the effects of lesions of the amygdala which arise at different stages of development on this key aspect of social cognition. Tests of ToM, executive and general neuropsychological…

Not Only Size Matters: Early-Talker and Late-Talker Vocabularies Support Different Word-Learning Biases in Babies and Networks.

PubMed

Colunga, Eliana; Sims, Clare E

2017-02-01

In typical development, word learning goes from slow and laborious to fast and seemingly effortless. Typically developing 2-year-olds seem to intuit the whole range of things in a category from hearing a single instance named-they have word-learning biases. This is not the case for children with relatively small vocabularies (late talkers). We present a computational model that accounts for the emergence of word-learning biases in children at both ends of the vocabulary spectrum based solely on vocabulary structure. The results of Experiment 1 show that late-talkers' and early-talkers' noun vocabularies have different structures and that neural networks trained on the vocabularies of individual late talkers acquire different word-learning biases than those trained on early-talker vocabularies. These models make novel predictions about the word-learning biases in these two populations. Experiment 2 tests these predictions on late- and early-talking toddlers in a novel noun generalization task. Copyright © 2016 Cognitive Science Society, Inc.

Alcohol exposure alters DNA methylation profiles in mouse embryos at early neurulation

PubMed Central

Liu, Yunlong; Balaraman, Yokesh; Wang, Guohua; Nephew, Kenneth P.; Zhou, Feng C.

2009-01-01

Alcohol exposure during development can cause variable neurofacial deficit and growth retardation known as fetal alcohol spectrum disorders (FASD). The mechanism underlying FASD is not fully understood. However, alcohol, which is known to affect methyl donor metabolism, may induce aberrant epigenetic changes contributing to FASD. Using a tightly controlled whole-embryo culture, we investigated the effect of alcohol exposure (88 mM) at early embryonic neurulation on genome-wide DNA methylation and gene expression in the C57BL/6 mouse. The DNA methylation landscape around promoter CpG islands at early mouse development was analyzed using MeDIP (methylated DNA immunoprecipitation) coupled with microarray (MeDIP-chip). At early neurulation, genes associated with high CpG promoters (HCP) had a lower ratio of methylation but a greater ratio of expression. Alcohol-induced alterations in DNA methylation were observed, particularly in genes on chromosomes 7, 10 and X; remarkably, a >10 fold increase in the number of genes with increased methylation on chromosomes 10 and X was observed in alcohol-exposed embryos with a neural tube defect phenotype compared to embryos without a neural tube defect. Significant changes in methylation were seen in imprinted genes, genes known to play roles in cell cycle, growth, apoptosis, cancer, and in a large number of genes associated with olfaction. Altered methylation was associated with significant (p < 0.01) changes in expression for 84 genes. Sequenom EpiTYPER DNA methylation analysis was used for validation of the MeDIP-chip data. Increased methylation of genes known to play a role in metabolism (Cyp4f13) and decreased methylation of genes associated with development (Nlgn3, Elavl2, Sox21 and Sim1), imprinting (Igf2r) and chromatin (Hist1h3d) was confirmed. In a mouse model for FASD, we show for the first time that alcohol exposure during early neurulation can induce aberrant changes in DNA methylation patterns with associated changes in gene expression, which together may contribute to the observed abnormal fetal development. PMID:20009564

Alcohol exposure alters DNA methylation profiles in mouse embryos at early neurulation.

PubMed

Liu, Yunlong; Balaraman, Yokesh; Wang, Guohua; Nephew, Kenneth P; Zhou, Feng C

2009-10-01

Alcohol exposure during development can cause variable neurofacial deficit and growth retardation known as fetal alcohol spectrum disorders (FASD). The mechanism underlying FASD is not fully understood. However, alcohol, which is known to affect methyl donor metabolism, may induce aberrant epigenetic changes contributing to FASD. Using a tightly controlled whole-embryo culture, we investigated the effect of alcohol exposure (88mM) at early embryonic neurulation on genome-wide DNA methylation and gene expression in the C57BL/6 mouse. The DNA methylation landscape around promoter CpG islands at early mouse development was analyzed using MeDIP (methylated DNA immunoprecipitation) coupled with microarray (MeDIP-chip). At early neurulation, genes associated with high CpG promoters (HCP) had a lower ratio of methylation but a greater ratio of expression. Alcohol-induced alterations in DNA methylation were observed, particularly in genes on chromosomes 7, 10, and X; remarkably, a >10 fold increase in the number of genes with increased methylation on chromosomes 10 and X was observed in alcohol-exposed embryos with a neural tube defect phenotype compared to embryos without a neural tube defect. Significant changes in methylation were seen in imprinted genes, genes known to play roles in cell cycle, growth, apoptosis, cancer, and in a large number of genes associated with olfaction. Altered methylation was associated with significant (p<0.01) changes in expression for 84 genes. Sequenom EpiTYPER DNA methylation analysis was used for validation of the MeDIP-chip data. Increased methylation of genes known to play a role in metabolism (Cyp4f13) and decreased methylation of genes associated with development (Nlgn3, Elavl2, Sox21 and Sim1), imprinting (Igf2r) and chromatin (Hist1h3d) was confirmed. In a mouse model for FASD, we show for the first time that alcohol exposure during early neurulation can induce aberrant changes in DNA methylation patterns with associated changes in gene expression, which together may contribute to the observed abnormal fetal development.

Penetration and differentiation of cephalic neural crest-derived cells in the developing mouse telencephalon.

PubMed

Yamanishi, Emiko; Takahashi, Masanori; Saga, Yumiko; Osumi, Noriko

2012-12-01

Neural crest (NC) cells originate from the neural folds and migrate into the various embryonic regions where they differentiate into multiple cell types. A population of cephalic neural crest-derived cells (NCDCs) penetrates back into the developing forebrain to differentiate into microvascular pericytes, but little is known about when and how cephalic NCDCs invade the telencephalon and differentiate into pericytes. Using a transgenic mouse line in which NCDCs are genetically labeled with enhanced green fluorescent protein (EGFP), we observed that NCDCs started to invade the telencephalon together with endothelial cells from embryonic day (E) 9.5. A majority of NCDCs located in the telencephalon expressed pericyte markers, that is, PDGFRβ and NG2, and differentiated into pericytes around E11.5. Surprisingly, many of the NC-derived pericytes express p75, an undifferentiated NCDC marker at E11.5, as well as NCDCs in the mesenchyme. At the same time, a minor population of NCDCs that located separately from blood vessels in the telencephalon were NG2-negative and some of these NCDCs also expressed p75. Proliferation and differentiation of pericytes appeared to occur in a specific mesenchymal region where blood vessels penetrated into the telencephalon. These results indicate that (i) NCDCs penetrate back into the telencephalon in parallel with angiogenesis, (ii) many NC-derived pericytes may be still in pre-mature states even though after differentiation into pericytes in the early developing stages, (iii) a small minority of NCDCs may retain undifferentiated states in the developing telencephalon, and (iv) a majority of NCDCs proliferate and differentiate into pericytes in the mesenchyme around the telencephalon. © 2012 The Authors Development, Growth & Differentiation © 2012 Japanese Society of Developmental Biologists.

Transcription factors in melanocyte development: distinct roles for Pax-3 and Mitf.

PubMed

Hornyak, T J; Hayes, D J; Chiu, L Y; Ziff, E B

2001-03-01

A transgenic mouse model was used to examine the roles of the murine transcription factors Pax-3 and Mitf in melanocyte development. Transgenic mice expressing beta-galactosidase from the dopachrome tautomerase (Dct) promoter were generated and found to express the transgene in developing melanoblasts as early as embryonic day (E) 9.5. These mice express the transgene in a pattern characteristic of endogenous Dct expression. Transgenic mice were intercrossed with two murine coat color mutants, Splotch (Sp), containing a mutation in the murine Pax3 gene, and Mitf(mi), with a mutation in the basic-helix-loop-helix-leucine zipper gene Mitf. Transgenic heterozygous mutant animals were crossed to generate transgenic embryos for analysis. Examination of beta-galactosidase-expressing melanoblasts in mutant embryos reveals that Mitf is required in vivo for survival of melanoblasts up to the migration staging area in neural crest development. Examination of Mitf(mi)/+ embryos shows that there are diminished numbers of melanoblasts in the heterozygous state early in melanocyte development, consistent with a gene dosage-dependent effect upon cell survival. However, quantification and analysis of melanoblast growth during the migratory phase suggests that melanoblasts then increase in number more rapidly in the heterozygous embryo. In contrast to Mitf(mi)/Mitf(mi) embryos, Sp/Sp embryos exhibit melanoblasts that have migrated to characteristic locations along the melanoblast migratory pathway, but are greatly reduced in number compared to control littermates. Together, these results support a model for melanocyte development whereby Pax3 is required to expand a pool of committed melanoblasts or restricted progenitor cells early in development, whereas Mitf facilitates survival of the melanoblast in a gene dosage-dependent manner within and immediately after emigration from the dorsal neural tube, and may also directly or indirectly affect the rate at which melanoblast number increases during dorsolateral pathway migration.

Network Analysis: Applications for the Developing Brain

PubMed Central

Chu-Shore, Catherine J.; Kramer, Mark A.; Bianchi, Matt T.; Caviness, Verne S.; Cash, Sydney S.

2011-01-01

Development of the human brain follows a complex trajectory of age-specific anatomical and physiological changes. The application of network analysis provides an illuminating perspective on the dynamic interregional and global properties of this intricate and complex system. Here, we provide a critical synopsis of methods of network analysis with a focus on developing brain networks. After discussing basic concepts and approaches to network analysis, we explore the primary events of anatomical cortical development from gestation through adolescence. Upon this framework, we describe early work revealing the evolution of age-specific functional brain networks in normal neurodevelopment. Finally, we review how these relationships can be altered in disease and perhaps even rectified with treatment. While this method of description and inquiry remains in early form, there is already substantial evidence that the application of network models and analysis to understanding normal and abnormal human neural development holds tremendous promise for future discovery. PMID:21303762

Protracted development of executive and mnemonic brain systems underlying working memory in adolescence: A longitudinal fMRI study.

PubMed

Simmonds, Daniel J; Hallquist, Michael N; Luna, Beatriz

2017-08-15

Working memory (WM), the ability to hold information on-line to guide planned behavior, improves through adolescence in parallel with continued maturation of critical brain systems supporting cognitive control. Initial developmental neuroimaging studies with one or two timepoints have provided important though varied results limiting our understanding of which and how neural systems change during this transition into mature WM. In this study, we leverage functional magnetic resonance imaging (fMRI) longitudinal data spanning up to 9 years in 129 normally developing individuals to identify which systems demonstrate growth changes that accompany improvements in WM performance. We used a memory guided saccade task that allowed us to probe encoding, pure maintenance, and retrieval neural processes of WM. Consistent with prior research, we found that WM performance continued to improve into the early 20's. fMRI region of interest (ROI) analyses revealed developmental (1) increases in sensorimotor-related (encoding/retrieval) activity in visual cortex from childhood through early adulthood that were associated with WM accuracy and (2) decreases in sustained (maintenance) activity in executive regions from childhood through mid-adolescence that were associated with response latency in childhood and early adolescence. Together these results provide compelling evidence that underlying the maturation of WM is a transition from reliance on executive systems to specialized regions related to the domain of mnemonic requirements of the task leading to optimal performance. Copyright © 2017. Published by Elsevier Inc.

Hippocampal Plasticity During the Progression of Alzheimer’s disease

PubMed Central

Mufson, Elliott J.; Mahady, Laura; Waters, Diana; Counts, Scott E.; Perez, Sylvia E.; DeKosky, Steven; Ginsberg, Stephen D.; Ikonomovic, Milos D.; Scheff, Stephen; Binder, Lester

2015-01-01

Neuroplasticity involves molecular changes in central nervous system (CNS) synaptic structure and function throughout life. The concept of neural organization allows for synaptic remodeling as a compensatory mechanism to the early pathobiology of Alzheimer’s disease (AD) in an attempt to maintain brain function and cognition during the onset of dementia. The hippocampus, a crucial component of the medial temporal lobe memory circuit, is affected early in AD and displays synaptic and intraneuronal molecular remodeling against a pathological background of extracellular amyloid-beta (Aβ) deposition and intracellular neurofibrillary tangle (NFT) formation in the early stages of AD. Here we discuss human clinical pathological findings supporting the concept that the hippocampus is capable of neural plasticity during mild cognitive impairment (MCI), a prodromal stage of AD and early stage AD. PMID:25772787

Future trends in Neuroimaging: Neural processes as expressed within real-life contexts

PubMed Central

Hasson, Uri; Honey, Christopher J.

2012-01-01

Human neuroscience research has changed dramatically with the proliferation and refinement of functional magnetic resonance imaging (fMRI) technologies. The early years of the technique were largely devoted to methods development and validation, and to the coarse-grained mapping of functional topographies. This paper will cover three emerging trends that we believe will be central to fMRI research in the coming decade. In the first section of this paper, we argue in favor of a shift from fine-grained functional labeling toward the characterization of underlying neural processes. In the second section, we examine three methodological developments that have improved our ability to characterize underlying neural processes using fMRI. In the last section, we highlight the trend towards more ecologically valid fMRI experiments, which engage neural circuits in real life conditions. We note that many of our cognitive faculties emerge from interpersonal interactions, and that a complete understanding of the cognitive processes within a single individual's brain cannot be achieved without understanding the interactions among individuals. Looking forward to the future of human fMRI, we conclude that the major constraint on new discoveries will not be related to the spatiotemporal resolution of the BOLD signal, which is constantly improving, but rather to the precision of our hypotheses and the creativity of our methods for testing them. PMID:22348879

Sex-related variation in human behavior and the brain

PubMed Central

Hines, Melissa

2010-01-01

Male and female fetuses differ in testosterone concentrations beginning as early as week 8 of gestation. This early hormone difference exerts permanent influences on brain development and behavior. Contemporary research shows that hormones are particularly important for the development of sex-typical childhood behavior, including toy choices, which until recently were thought to result solely from sociocultural influences. Prenatal testosterone exposure also appears to influence sexual orientation and gender identity, as well as some, but not all, sex-related cognitive, motor and personality characteristics. Neural mechanisms responsible for these hormone-induced behavioral outcomes are beginning to be identified, and current evidence suggests involvement of the hypothalamus and amygdala, as well as interhemispheric connectivity, and cortical areas involved in visual processing. PMID:20724210

Neural Processing of Facial Identity and Emotion in Infants at High-Risk for Autism Spectrum Disorders

PubMed Central

Fox, Sharon E.; Wagner, Jennifer B.; Shrock, Christine L.; Tager-Flusberg, Helen; Nelson, Charles A.

2013-01-01

Deficits in face processing and social impairment are core characteristics of autism spectrum disorder. The present work examined 7-month-old infants at high-risk for developing autism and typically developing controls at low-risk, using a face perception task designed to differentiate between the effects of face identity and facial emotions on neural response using functional Near-Infrared Spectroscopy. In addition, we employed independent component analysis, as well as a novel method of condition-related component selection and classification to identify group differences in hemodynamic waveforms and response distributions associated with face and emotion processing. The results indicate similarities of waveforms, but differences in the magnitude, spatial distribution, and timing of responses between groups. These early differences in local cortical regions and the hemodynamic response may, in turn, contribute to differences in patterns of functional connectivity. PMID:23576966

Movement maintains forebrain neurogenesis via peripheral neural feedback in larval zebrafish

PubMed Central

Hall, Zachary Jonas

2018-01-01

The postembryonic brain exhibits experience-dependent development, in which sensory experience guides normal brain growth. This neuroplasticity is thought to occur primarily through structural and functional changes in pre-existing neurons. Whether neurogenesis also mediates the effects of experience on brain growth is unclear. Here, we characterized the importance of motor experience on postembryonic neurogenesis in larval zebrafish. We found that movement maintains an expanded pool of forebrain neural precursors by promoting progenitor self-renewal over the production of neurons. Physical cues associated with swimming (bodily movement) increase neurogenesis and these cues appear to be conveyed by dorsal root ganglia (DRG) in the zebrafish body: DRG-deficient larvae exhibit attenuated neurogenic responses to movement and targeted photoactivation of DRG in immobilized larvae expands the pallial pool of proliferative cells. Our results demonstrate the importance of movement in neurogenic brain growth and reveal a fundamental sensorimotor association that may couple early motor and brain development. PMID:29528285

Dynamic expression of the LAP family of genes during early development of Xenopus tropicalis.

PubMed

Yang, Qiutan; Lv, Xiaoyan; Kong, Qinghua; Li, Chaocui; Zhou, Qin; Mao, Bingyu

2011-10-01

The leucine-rich repeats and PDZ (LAP) family of genes are crucial for the maintenance of cell polarity as well as for epithelial homeostasis and tumor suppression in both vertebrates and invertebrates. Four members of this gene family are known: densin, erbin, scribble and lano. Here, we identified the four members of the LAP gene family in Xenopus tropicalis and studied their expression patterns during embryonic development. The Xenopus LAP proteins show a conserved domain structure that is similar to their homologs in other vertebrates. In Xenopus embryos, these genes were detected in animal cap cells at the early gastrula stage. At later stages of development, they were widely expressed in epithelial tissues that are highly polar in nature, including the neural epithelia, optic and otic vesicles, and in the pronephros. These data suggest that the roles of the Xenopus LAP genes in the control of cell polarity and morphogenesis are conserved during early development. Erbin and lano show similar expression patterns in the developing head, suggesting potential functional interactions between the two molecules in vivo.

Neural preservation underlies speech improvement from auditory deprivation in young cochlear implant recipients.

PubMed

Feng, Gangyi; Ingvalson, Erin M; Grieco-Calub, Tina M; Roberts, Megan Y; Ryan, Maura E; Birmingham, Patrick; Burrowes, Delilah; Young, Nancy M; Wong, Patrick C M

2018-01-30

Although cochlear implantation enables some children to attain age-appropriate speech and language development, communicative delays persist in others, and outcomes are quite variable and difficult to predict, even for children implanted early in life. To understand the neurobiological basis of this variability, we used presurgical neural morphological data obtained from MRI of individual pediatric cochlear implant (CI) candidates implanted younger than 3.5 years to predict variability of their speech-perception improvement after surgery. We first compared neuroanatomical density and spatial pattern similarity of CI candidates to that of age-matched children with normal hearing, which allowed us to detail neuroanatomical networks that were either affected or unaffected by auditory deprivation. This information enables us to build machine-learning models to predict the individual children's speech development following CI. We found that regions of the brain that were unaffected by auditory deprivation, in particular the auditory association and cognitive brain regions, produced the highest accuracy, specificity, and sensitivity in patient classification and the most precise prediction results. These findings suggest that brain areas unaffected by auditory deprivation are critical to developing closer to typical speech outcomes. Moreover, the findings suggest that determination of the type of neural reorganization caused by auditory deprivation before implantation is valuable for predicting post-CI language outcomes for young children.

High glucose environment inhibits cranial neural crest survival by activating excessive autophagy in the chick embryo

PubMed Central

Wang, Xiao-Yu; Li, Shuai; Wang, Guang; Ma, Zheng-Lai; Chuai, Manli; Cao, Liu; Yang, Xuesong

2015-01-01

High glucose levels induced by maternal diabetes could lead to defects in neural crest development during embryogenesis, but the cellular mechanism is still not understood. In this study, we observed a defect in chick cranial skeleton, especially parietal bone development in the presence of high glucose levels, which is derived from cranial neural crest cells (CNCC). In early chick embryo, we found that inducing high glucose levels could inhibit the development of CNCC, however, cell proliferation was not significantly involved. Nevertheless, apoptotic CNCC increased in the presence of high levels of glucose. In addition, the expression of apoptosis and autophagy relevant genes were elevated by high glucose treatment. Next, the application of beads soaked in either an autophagy stimulator (Tunicamycin) or inhibitor (Hydroxychloroquine) functionally proved that autophagy was involved in regulating the production of CNCC in the presence of high glucose levels. Our observations suggest that the ERK pathway, rather than the mTOR pathway, most likely participates in mediating the autophagy induced by high glucose. Taken together, our observations indicated that exposure to high levels of glucose could inhibit the survival of CNCC by affecting cell apoptosis, which might result from the dysregulation of the autophagic process. PMID:26671447

An Integrative Model for the Neural Mechanism of Eye Movement Desensitization and Reprocessing (EMDR)

PubMed Central

Coubard, Olivier A.

2016-01-01

Since the seminal report by Shapiro that bilateral stimulation induces cognitive and emotional changes, 26 years of basic and clinical research have examined the effects of Eye Movement Desensitization and Reprocessing (EMDR) in anxiety disorders, particularly in post-traumatic stress disorder (PTSD). The present article aims at better understanding EMDR neural mechanism. I first review procedural aspects of EMDR protocol and theoretical hypothesis about EMDR effects, and develop the reasons why the scientific community is still divided about EMDR. I then slide from psychology to physiology describing eye movements/emotion interaction from the physiological viewpoint, and introduce theoretical and technical tools used in movement research to re-examine EMDR neural mechanism. Using a recent physiological model for the neuropsychological architecture of motor and cognitive control, the Threshold Interval Modulation with Early Release-Rate of rIse Deviation with Early Release (TIMER-RIDER)—model, I explore how attentional control and bilateral stimulation may participate to EMDR effects. These effects may be obtained by two processes acting in parallel: (i) activity level enhancement of attentional control component; and (ii) bilateral stimulation in any sensorimotor modality, both resulting in lower inhibition enabling dysfunctional information to be processed and anxiety to be reduced. The TIMER-RIDER model offers quantitative predictions about EMDR effects for future research about its underlying physiological mechanisms. PMID:27092064

Downregulation of ribosome biogenesis during early forebrain development

PubMed Central

Chau, Kevin F; Shannon, Morgan L; Fame, Ryann M; Fonseca, Erin; Mullan, Hillary; Johnson, Matthew B; Sendamarai, Anoop K; Springel, Mark W; Laurent, Benoit

2018-01-01

Forebrain precursor cells are dynamic during early brain development, yet the underlying molecular changes remain elusive. We observed major differences in transcriptional signatures of precursor cells from mouse forebrain at embryonic days E8.5 vs. E10.5 (before vs. after neural tube closure). Genes encoding protein biosynthetic machinery were strongly downregulated at E10.5. This was matched by decreases in ribosome biogenesis and protein synthesis, together with age-related changes in proteomic content of the adjacent fluids. Notably, c-MYC expression and mTOR pathway signaling were also decreased at E10.5, providing potential drivers for the effects on ribosome biogenesis and protein synthesis. Interference with c-MYC at E8.5 prematurely decreased ribosome biogenesis, while persistent c-MYC expression in cortical progenitors increased transcription of protein biosynthetic machinery and enhanced ribosome biogenesis, as well as enhanced progenitor proliferation leading to subsequent macrocephaly. These findings indicate large, coordinated changes in molecular machinery of forebrain precursors during early brain development. PMID:29745900

Perturbed neural activity disrupts cerebral angiogenesis during a postnatal critical period

PubMed Central

Whiteus, Christina; Freitas, Catarina; Grutzendler, Jaime

2013-01-01

During the neonatal period, activity-dependent neural circuit remodeling coincides with growth and refinement of the cerebral microvasculature1,2. Whether neural activity also influences the patterning of the vascular bed is not known. Here we show in neonatal mice, that neither reduction of sensory input through whisker trimming nor moderately increased activity by environmental enrichment affected cortical microvascular development. Surprisingly however, chronic stimulation by repetitive sounds, whisker deflection, or motor activity led to a near arrest of angiogenesis in barrel, auditory, and motor cortices, respectively. Chemically-induced seizures also caused robust reductions in microvascular density. Altering neural activity in adult mice, however, did not affect the vasculature. Histological analysis and time-lapse in vivo two-photon microscopy revealed that hyperactivity did not lead to cell death or pruning of existing vessels but rather reduced endothelial proliferation and vessel sprouting. This anti-angiogenic effect was prevented by administration of the nitric oxide synthase (NOS) inhibitor L-NAME and in mice with neuronal and inducible NOS deficiency, suggesting that excessive nitric oxide released from hyperactive interneurons and glia inhibited vessel growth. Vascular deficits persisted long after cessation of hyperstimulation, providing evidence for a critical period after which proper microvascular patterning cannot be re-established. Reduced microvascular density diminished the ability of the brain to compensate for hypoxic challenges, leading to dendritic spine loss in regions distant from capillaries. Therefore, excessive sensorimotor stimulation and repetitive neural activation during early childhood may cause lifelong deficits in microvascular reserve, which could have important consequences on brain development, function, and pathology. PMID:24305053

Perturbed neural activity disrupts cerebral angiogenesis during a postnatal critical period.

PubMed

Whiteus, Christina; Freitas, Catarina; Grutzendler, Jaime

2014-01-16

During the neonatal period, activity-dependent neural-circuit remodelling coincides with growth and refinement of the cerebral microvasculature. Whether neural activity also influences the patterning of the vascular bed is not known. Here we show in neonatal mice, that neither reduction of sensory input through whisker trimming nor moderately increased activity by environmental enrichment affects cortical microvascular development. Unexpectedly, chronic stimulation by repetitive sounds, whisker deflection or motor activity led to a near arrest of angiogenesis in barrel, auditory and motor cortices, respectively. Chemically induced seizures also caused robust reductions in microvascular density. However, altering neural activity in adult mice did not affect the vasculature. Histological analysis and time-lapse in vivo two-photon microscopy revealed that hyperactivity did not lead to cell death or pruning of existing vessels but rather to reduced endothelial proliferation and vessel sprouting. This anti-angiogenic effect was prevented by administration of the nitric oxide synthase (NOS) inhibitor L-NAME and in mice with neuronal and inducible NOS deficiency, suggesting that excessive nitric oxide released from hyperactive interneurons and glia inhibited vessel growth. Vascular deficits persisted long after cessation of hyperstimulation, providing evidence for a critical period after which proper microvascular patterning cannot be re-established. Reduced microvascular density diminished the ability of the brain to compensate for hypoxic challenges, leading to dendritic spine loss in regions distant from capillaries. Therefore, excessive sensorimotor stimulation and repetitive neural activation during early childhood may cause lifelong deficits in microvascular reserve, which could have important consequences for brain development, function and pathology.

Development of neural responsivity to vocal sounds in higher level auditory cortex of songbirds

PubMed Central

Miller-Sims, Vanessa C.

2014-01-01

Like humans, songbirds learn vocal sounds from “tutors” during a sensitive period of development. Vocal learning in songbirds therefore provides a powerful model system for investigating neural mechanisms by which memories of learned vocal sounds are stored. This study examined whether NCM (caudo-medial nidopallium), a region of higher level auditory cortex in songbirds, serves as a locus where a neural memory of tutor sounds is acquired during early stages of vocal learning. NCM neurons respond well to complex auditory stimuli, and evoked activity in many NCM neurons habituates such that the response to a stimulus that is heard repeatedly decreases to approximately one-half its original level (stimulus-specific adaptation). The rate of neural habituation serves as an index of familiarity, being low for familiar sounds, but high for novel sounds. We found that response strength across different song stimuli was higher in NCM neurons of adult zebra finches than in juveniles, and that only adult NCM responded selectively to tutor song. The rate of habituation across both tutor song and novel conspecific songs was lower in adult than in juvenile NCM, indicating higher familiarity and a more persistent response to song stimuli in adults. In juvenile birds that have memorized tutor vocal sounds, neural habituation was higher for tutor song than for a familiar conspecific song. This unexpected result suggests that the response to tutor song in NCM at this age may be subject to top-down influences that maintain the tutor song as a salient stimulus, despite its high level of familiarity. PMID:24694936

Meninges: from protective membrane to stem cell niche.

PubMed

Decimo, Ilaria; Fumagalli, Guido; Berton, Valeria; Krampera, Mauro; Bifari, Francesco

2012-01-01

Meninges are a three tissue membrane primarily known as coverings of the brain. More in depth studies on meningeal function and ultrastructure have recently changed the view of meninges as a merely protective membrane. Accurate evaluation of the anatomical distribution in the CNS reveals that meninges largely penetrate inside the neural tissue. Meninges enter the CNS by projecting between structures, in the stroma of choroid plexus and form the perivascular space (Virchow-Robin) of every parenchymal vessel. Thus, meninges may modulate most of the physiological and pathological events of the CNS throughout the life. Meninges are present since the very early embryonic stages of cortical development and appear to be necessary for normal corticogenesis and brain structures formation. In adulthood meninges contribute to neural tissue homeostasis by secreting several trophic factors including FGF2 and SDF-1. Recently, for the first time, we have identified the presence of a stem cell population with neural differentiation potential in meninges. In addition, we and other groups have further described the presence in meninges of injury responsive neural precursors. In this review we will give a comprehensive view of meninges and their multiple roles in the context of a functional network with the neural tissue. We will highlight the current literature on the developmental feature of meninges and their role in cortical development. Moreover, we will elucidate the anatomical distribution of the meninges and their trophic properties in adult CNS. Finally, we will emphasize recent evidences suggesting the potential role of meninges as stem cell niche harbouring endogenous precursors that can be activated by injury and are able to contribute to CNS parenchymal reaction.

Artificial Neural Network-Based Early-Age Concrete Strength Monitoring Using Dynamic Response Signals.

PubMed

Kim, Junkyeong; Lee, Chaggil; Park, Seunghee

2017-06-07

Concrete is one of the most common materials used to construct a variety of civil infrastructures. However, since concrete might be susceptible to brittle fracture, it is essential to confirm the strength of concrete at the early-age stage of the curing process to prevent unexpected collapse. To address this issue, this study proposes a novel method to estimate the early-age strength of concrete, by integrating an artificial neural network algorithm with a dynamic response measurement of the concrete material. The dynamic response signals of the concrete, including both electromechanical impedances and guided ultrasonic waves, are obtained from an embedded piezoelectric sensor module. The cross-correlation coefficient of the electromechanical impedance signals and the amplitude of the guided ultrasonic wave signals are selected to quantify the variation in dynamic responses according to the strength of the concrete. Furthermore, an artificial neural network algorithm is used to verify a relationship between the variation in dynamic response signals and concrete strength. The results of an experimental study confirm that the proposed approach can be effectively applied to estimate the strength of concrete material from the early-age stage of the curing process.

Artificial Neural Network-Based Early-Age Concrete Strength Monitoring Using Dynamic Response Signals

PubMed Central

Kim, Junkyeong; Lee, Chaggil; Park, Seunghee

2017-01-01

Concrete is one of the most common materials used to construct a variety of civil infrastructures. However, since concrete might be susceptible to brittle fracture, it is essential to confirm the strength of concrete at the early-age stage of the curing process to prevent unexpected collapse. To address this issue, this study proposes a novel method to estimate the early-age strength of concrete, by integrating an artificial neural network algorithm with a dynamic response measurement of the concrete material. The dynamic response signals of the concrete, including both electromechanical impedances and guided ultrasonic waves, are obtained from an embedded piezoelectric sensor module. The cross-correlation coefficient of the electromechanical impedance signals and the amplitude of the guided ultrasonic wave signals are selected to quantify the variation in dynamic responses according to the strength of the concrete. Furthermore, an artificial neural network algorithm is used to verify a relationship between the variation in dynamic response signals and concrete strength. The results of an experimental study confirm that the proposed approach can be effectively applied to estimate the strength of concrete material from the early-age stage of the curing process. PMID:28590456

Cross-Modal Multivariate Pattern Analysis

PubMed Central

Meyer, Kaspar; Kaplan, Jonas T.

2011-01-01

Multivariate pattern analysis (MVPA) is an increasingly popular method of analyzing functional magnetic resonance imaging (fMRI) data1-4. Typically, the method is used to identify a subject's perceptual experience from neural activity in certain regions of the brain. For instance, it has been employed to predict the orientation of visual gratings a subject perceives from activity in early visual cortices5 or, analogously, the content of speech from activity in early auditory cortices6. Here, we present an extension of the classical MVPA paradigm, according to which perceptual stimuli are not predicted within, but across sensory systems. Specifically, the method we describe addresses the question of whether stimuli that evoke memory associations in modalities other than the one through which they are presented induce content-specific activity patterns in the sensory cortices of those other modalities. For instance, seeing a muted video clip of a glass vase shattering on the ground automatically triggers in most observers an auditory image of the associated sound; is the experience of this image in the "mind's ear" correlated with a specific neural activity pattern in early auditory cortices? Furthermore, is this activity pattern distinct from the pattern that could be observed if the subject were, instead, watching a video clip of a howling dog? In two previous studies7,8, we were able to predict sound- and touch-implying video clips based on neural activity in early auditory and somatosensory cortices, respectively. Our results are in line with a neuroarchitectural framework proposed by Damasio9,10, according to which the experience of mental images that are based on memories - such as hearing the shattering sound of a vase in the "mind's ear" upon seeing the corresponding video clip - is supported by the re-construction of content-specific neural activity patterns in early sensory cortices. PMID:22105246

Cognitive influences on self-care decision making in persons with heart failure.

PubMed

Dickson, Victoria V; Tkacs, Nancy; Riegel, Barbara

2007-09-01

Despite advances in management, heart failure is associated with high rates of hospitalization, poor quality of life, and early death. Education intended to improve patients' abilities to care for themselves is an integral component of disease management programs. True self-care requires that patients make decisions about symptoms, but the cognitive deficits documented in 30% to 50% of the heart failure population may make daily decision making challenging. After describing heart failure self-care as a naturalistic decision making process, we explore cognitive deficits known to exist in persons with heart failure. Problems in heart failure self-care are analyzed in relation to neural alterations associated with heart failure. As a neural process, decision making has been traced to regions of the prefrontal cortex, the same areas that are affected by ischemia, infarction, and hypoxemia in heart failure. Resulting deficits in memory, attention, and executive function may impair the perception and interpretation of early symptoms and reasoning and, thereby, delay early treatment implementation. There is compelling evidence that the neural processes critical to decision making are located in the same structures that are affected by heart failure. Because self-care requires the cognitive ability to learn, perceive, interpret, and respond, research is needed to discern how neural deficits affects these abilities, decision-making, and self-care behaviors.

Inter-subject synchrony as an index of functional specialization in early childhood.

PubMed

Moraczewski, Dustin; Chen, Gang; Redcay, Elizabeth

2018-02-02

Early childhood is a time of significant change within multiple cognitive domains including social cognition, memory, executive function, and language; however, the corresponding neural changes remain poorly understood. This is likely due to the difficulty in acquiring artifact-free functional MRI data during complex task-based or unconstrained resting-state experiments in young children. In addition, task-based and resting state experiments may not capture dynamic real-world processing. Here we overcome both of these challenges through use of naturalistic viewing (i.e., passively watching a movie in the scanner) combined with inter-subject neural synchrony to examine functional specialization within 4- and 6-year old children. Using a novel and stringent crossed random effect statistical analysis, we find that children show more variable patterns of activation compared to adults, particularly within regions of the default mode network (DMN). In addition, we found partial evidence that child-to-adult synchrony increased as a function of age within a DMN region: the temporoparietal junction. Our results suggest age-related differences in functional brain organization within a cross-sectional sample during an ecologically valid context and demonstrate that neural synchrony during naturalistic viewing fMRI can be used to examine functional specialization during early childhood - a time when neural and cognitive systems are in flux.

Characterization of Early Cortical Neural Network ...

EPA Pesticide Factsheets

We examined the development of neural network activity using microelectrode array (MEA) recordings made in multi-well MEA plates (mwMEAs) over the first 12 days in vitro (DIV). In primary cortical cultures made from postnatal rats, action potential spiking activity was essentially absent on DIV 2 and developed rapidly between DIV 5 and 12. Spiking activity was primarily sporadic and unorganized at early DIV, and became progressively more organized with time in culture, with bursting parameters, synchrony and network bursting increasing between DIV 5 and 12. We selected 12 features to describe network activity and principal components analysis using these features demonstrated a general segregation of data by age at both the well and plate levels. Using a combination of random forest classifiers and Support Vector Machines, we demonstrated that 4 features (CV of within burst ISI, CV of IBI, network spike rate and burst rate) were sufficient to predict the age (either DIV 5, 7, 9 or 12) of each well recording with >65% accuracy. When restricting the classification problem to a binary decision, we found that classification improved dramatically, e.g. 95% accuracy for discriminating DIV 5 vs DIV 12 wells. Further, we present a novel resampling approach to determine the number of wells that might be needed for conducting comparisons of different treatments using mwMEA plates. Overall, these results demonstrate that network development on mwMEA plates is similar to

Infant visual attention and object recognition.

PubMed

Reynolds, Greg D

2015-05-15

This paper explores the role visual attention plays in the recognition of objects in infancy. Research and theory on the development of infant attention and recognition memory are reviewed in three major sections. The first section reviews some of the major findings and theory emerging from a rich tradition of behavioral research utilizing preferential looking tasks to examine visual attention and recognition memory in infancy. The second section examines research utilizing neural measures of attention and object recognition in infancy as well as research on brain-behavior relations in the early development of attention and recognition memory. The third section addresses potential areas of the brain involved in infant object recognition and visual attention. An integrated synthesis of some of the existing models of the development of visual attention is presented which may account for the observed changes in behavioral and neural measures of visual attention and object recognition that occur across infancy. Copyright © 2015 Elsevier B.V. All rights reserved.

Beyond Fluorescent Proteins: Hybrid and Bioluminescent Indicators for Imaging Neural Activities.

PubMed

Wang, Anqi; Feng, Jiesi; Li, Yulong; Zou, Peng

2018-04-18

Optical biosensors have been invaluable tools in neuroscience research, as they provide the ability to directly visualize neural activity in real time, with high specificity, and with exceptional spatial and temporal resolution. Notably, a majority of these sensors are based on fluorescent protein scaffolds, which offer the ability to target specific cell types or even subcellular compartments. However, fluorescent proteins are intrinsically bulky tags, often insensitive to the environment, and always require excitation light illumination. To address these limitations, there has been a proliferation of alternative sensor scaffolds developed in recent years, including hybrid sensors that combine the advantages of synthetic fluorophores and genetically encoded protein tags, as well as bioluminescent probes. While still in their early stage of development as compared with fluorescent protein-based sensors, these novel probes have offered complementary solutions to interrogate various aspects of neuronal communication, including transmitter release, changes in membrane potential, and the production of second messengers. In this Review, we discuss these important new developments with a particular focus on design strategies.

The Development of Animal Behavior: From Lorenz to Neural Nets

NASA Astrophysics Data System (ADS)

Bolhuis, Johan J.

In the study of behavioral development both causal and functional approaches have been used, and they often overlap. The concept of ontogenetic adaptations suggests that each developmental phase involves unique adaptations to the environment of the developing animal. The functional concept of optimal outbreeding has led to further experimental evidence and theoretical models concerning the role of sexual imprinting in the evolutionary process of sexual selection. From a causal perspective it has been proposed that behavioral ontogeny involves the development of various kinds of perceptual, motor, and central mechanisms and the formation of connections among them. This framework has been tested for a number of complex behavior systems such as hunger and dustbathing. Imprinting is often seen as a model system for behavioral development in general. Recent advances in imprinting research have been the result of an interdisciplinary effort involving ethology, neuroscience, and experimental psychology, with a continual interplay between these approaches. The imprinting results are consistent with Lorenz' early intuitive suggestions and are also reflected in the architecture of recent neural net models.

Identification of the actual state and entity availability forecasting in power engineering using neural-network technologies

NASA Astrophysics Data System (ADS)

Protalinsky, O. M.; Shcherbatov, I. A.; Stepanov, P. V.

2017-11-01

A growing number of severe accidents in RF call for the need to develop a system that could prevent emergency situations. In a number of cases accident rate is stipulated by careless inspections and neglects in developing repair programs. Across the country rates of accidents are growing because of a so-called “human factor”. In this regard, there has become urgent the problem of identification of the actual state of technological facilities in power engineering using data on engineering processes running and applying artificial intelligence methods. The present work comprises four model states of manufacturing equipment of engineering companies: defect, failure, preliminary situation, accident. Defect evaluation is carried out using both data from SCADA and ASEPCR and qualitative information (verbal assessments of experts in subject matter, photo- and video materials of surveys processed using pattern recognition methods in order to satisfy the requirements). Early identification of defects makes possible to predict the failure of manufacturing equipment using mathematical techniques of artificial neural network. In its turn, this helps to calculate predicted characteristics of reliability of engineering facilities using methods of reliability theory. Calculation of the given parameters provides the real-time estimation of remaining service life of manufacturing equipment for the whole operation period. The neural networks model allows evaluating possibility of failure of a piece of equipment consistent with types of actual defects and their previous reasons. The article presents the grounds for a choice of training and testing samples for the developed neural network, evaluates the adequacy of the neural networks model, and shows how the model can be used to forecast equipment failure. There have been carried out simulating experiments using a computer and retrospective samples of actual values for power engineering companies. The efficiency of the developed model for different types of manufacturing equipment has been proved. There have been offered other research areas in terms of the presented subject matter.

Old Dogs Learning New Tricks: Neuroplasticity Beyond the Juvenile Period

PubMed Central

Lillard, Angeline S.; Erisir, Alev

2014-01-01

Twenty years ago, the prevalent view in psychology was that although learning and the formation of new memories are lifelong occurrences, the neural changes associated with these events were all in the existing receptors. No new neural hardware, from synapses to neurons, was thought to appear after a protracted period early in life. In the past 20 years, another view has supplanted this one, showing that although the juvenile period is especially suited to neuroplastic adaptation, there is hard neuroplastic change later in life as well. We review a selection of evidence for this view from both animal and human models, showing how it reflects three principles of neuroplasticity: 1) earlier and later experience-induced changes to neuroarchitecture differ in degree more so than in type; 2) the types of experiences that lead to neuroplastic change narrow with age; and 3) differences in the amenability of neural circuitry to change result from basic differences in neuroarchitecture and neuroenvironment in different phases of development. PMID:24648605

The lighter side of BDNF

PubMed Central

Noble, Emily E.; Billington, Charles J.; Kotz, Catherine M.

2011-01-01

Brain-derived neurotrophic factor (BDNF) mediates energy metabolism and feeding behavior. As a neurotrophin, BDNF promotes neuronal differentiation, survival during early development, adult neurogenesis, and neural plasticity; thus, there is the potential that BDNF could modify circuits important to eating behavior and energy expenditure. The possibility that “faulty” circuits could be remodeled by BDNF is an exciting concept for new therapies for obesity and eating disorders. In the hypothalamus, BDNF and its receptor, tropomyosin-related kinase B (TrkB), are extensively expressed in areas associated with feeding and metabolism. Hypothalamic BDNF and TrkB appear to inhibit food intake and increase energy expenditure, leading to negative energy balance. In the hippocampus, the involvement of BDNF in neural plasticity and neurogenesis is important to learning and memory, but less is known about how BDNF participates in energy homeostasis. We review current research about BDNF in specific brain locations related to energy balance, environmental, and behavioral influences on BDNF expression and the possibility that BDNF may influence energy homeostasis via its role in neurogenesis and neural plasticity. PMID:21346243

The neurodevelopment of human sexual orientation.

PubMed

Rahman, Qazi

2005-01-01

One of the most enduring and controversial questions in the neuroscience of sexual behaviour surrounds the mechanisms which produce sexual attraction to either males or females. Here, evidence is reviewed which supports the proposal that sexual orientation in humans may be laid down in neural circuitry during early foetal development. Behaviour genetic investigations provide strong evidence for a heritable component to male and female sexual orientation. Linkage studies are partly suggestive of X-linked loci although candidate gene studies have produced null findings. Further evidence demonstrates a role for prenatal sex hormones which may influence the development of a putative network of sexual-orientation-related neural substrates. However, hormonal effects are often inconsistent and investigations rely heavily on 'proxy markers'. A consistent fraternal birth order effect in male sexual orientation also provides support for a model of maternal immunization processes affecting prenatal sexual differentiation. The notion that non-heterosexual preferences may reflect generalized neurodevelopmental perturbations is not supported by available data. These current theories have left little room for learning models of sexual orientation. Future investigations, across the neurosciences, should focus to elucidate the fundamental neural architecture underlying the target-specific direction of human sexual orientation, and their antecedents in developmental neurobiology.

Live Imaging of Adult Neural Stem Cells in Rodents

PubMed Central

Ortega, Felipe; Costa, Marcos R.

2016-01-01

The generation of cells of the neural lineage within the brain is not restricted to early development. New neurons, oligodendrocytes, and astrocytes are produced in the adult brain throughout the entire murine life. However, despite the extensive research performed in the field of adult neurogenesis during the past years, fundamental questions regarding the cell biology of adult neural stem cells (aNSCs) remain to be uncovered. For instance, it is crucial to elucidate whether a single aNSC is capable of differentiating into all three different macroglial cell types in vivo or these distinct progenies constitute entirely separate lineages. Similarly, the cell cycle length, the time and mode of division (symmetric vs. asymmetric) that these cells undergo within their lineage progression are interesting questions under current investigation. In this sense, live imaging constitutes a valuable ally in the search of reliable answers to the previous questions. In spite of the current limitations of technology new approaches are being developed and outstanding amount of knowledge is being piled up providing interesting insights in the behavior of aNSCs. Here, we will review the state of the art of live imaging as well as the alternative models that currently offer new answers to critical questions. PMID:27013941

Neural Correlates of Attentional Processing of Threat in Youth with and without Anxiety Disorders.

PubMed

Bechor, Michele; Ramos, Michelle L; Crowley, Michael J; Silverman, Wendy K; Pettit, Jeremy W; Reeb-Sutherland, Bethany C

2018-04-02

Late-stage attentional processing of threatening stimuli, quantified through event-related potentials (ERPs), differentiates youth with and without anxiety disorders. It is unknown whether early-stage attentional processing of threatening stimuli differentiates these groups. Examining both early and late stage attentional processes in youth may advance knowledge and enhance efforts to identify biomarkers for translational prevention and treatment research. Twenty-one youth with primary DSM-IV-TR anxiety disorders (10 males, ages 8-15 years) and 21 typically developing Controls (15 males, ages 8-16 years) completed a dot probe task while electroencephalography (EEG) was recorded, and ERPs were examined. Youth with anxiety disorders showed significantly larger (more positive) P1 amplitudes for threatening stimuli than for neutral stimuli, and Controls showed the opposite pattern. Youth with anxiety showed larger (more negative) N170 amplitudes compared with Controls. Controls showed significantly larger (more positive) P2 and P3 amplitudes, regardless of stimuli valence, compared with youth with anxiety disorders. ERPs observed during the dot probe task indicate youth with anxiety disorders display distinct neural processing during early stage attentional orienting and processing of faces; this was not the case for Controls. Such results suggest these ERP components may have potential as biomarkers of anxiety disorders in youth.

Age associations with neural processing of reward anticipation in adolescents with bipolar disorders

PubMed Central

Urošević, Snežana; Luciana, Monica; Jensen, Jonathan B.; Youngstrom, Eric A.; Thomas, Kathleen M.

2016-01-01

Reward/behavioral approach system hypersensitivity is implicated in bipolar disorders (BD) and in normative development during adolescence. Pediatric onset of BD is associated with a more severe illness course. However, little is known about neural processing of rewards in adolescents with BD or developmental (i.e., age) associations with activation of these neural systems. The present study aims to address this knowledge gap. The present sample included 21 adolescents with BD and 26 healthy adolescents, ages 13 to 19. Participants completed a functional magnetic resonance imaging (fMRI) protocol using the Monetary Incentive Delay (MID) task. Behavioral performance was similar between groups. Group differences in BOLD activation during target anticipation and feedback anticipation periods of the task were examined using whole-brain analyses, as were group differences in age effects. During both target anticipation and feedback anticipation, adolescents with BD, compared to adolescents without psychopathology, exhibited decreased engagement of frontal regions involved in cognitive control (i.e., dorsolateral prefrontal cortex). Healthy adolescents exhibited age-related decreases, while adolescents with BD exhibited age-related increases, in activity of other cognitive control frontal areas (i.e., right inferior frontal gyrus), suggesting altered development in the BD group. Longitudinal research is needed to examine potentially abnormal development of cognitive control during reward pursuit in adolescent BD and whether early therapeutic interventions can prevent these potential deviations from normative development. PMID:27114896

Developmental regulation of fear learning and anxiety behavior by endocannabinoids

PubMed Central

Lee, Tiffany T.-Y.; Hill, Matthew N.; Lee, Francis S.

2015-01-01

The developing brain undergoes substantial maturation into adulthood and the development of specific neural structures occurs on differing timelines. Transient imbalances between developmental trajectories of corticolimbic structures, which are known to contribute to regulation over fear learning and anxiety, can leave an individual susceptible to mental illness, particularly anxiety disorders. There is a substantial body of literature indicating that the endocannabinoid system critically regulates stress responsivity and emotional behavior throughout the life span, making this system a novel therapeutic target for stress- and anxiety-related disorders. During early life and adolescence, corticolimbic endocannabinoid signaling changes dynamically and coincides with different sensitive periods of fear learning, suggesting that endocannabinoid signaling underlies age-specific fear learning responses. Moreover, perturbations to these normative fluctuations in corticolimbic endocannabinoid signaling, such as stress or cannabinoid exposure, could serve as a neural substrate contributing to alterations to the normative developmental trajectory of neural structures governing emotional behavior and fear learning. In this review, we first introduce the components of the endocannabinoid system and discuss clinical and rodent models demonstrating endocannabinoid regulation of fear learning and anxiety in adulthood. Next, we highlight distinct fear learning and regulation profiles throughout development and discuss the ontogeny of the endocannabinoid system in the central nervous system, and models of pharmacological augmentation of endocannabinoid signaling during development in the context of fear learning and anxiety. PMID:26419643

Age associations with neural processing of reward anticipation in adolescents with bipolar disorders.

PubMed

Urošević, Snežana; Luciana, Monica; Jensen, Jonathan B; Youngstrom, Eric A; Thomas, Kathleen M

2016-01-01

Reward/behavioral approach system hypersensitivity is implicated in bipolar disorders (BD) and in normative development during adolescence. Pediatric onset of BD is associated with a more severe illness course. However, little is known about neural processing of rewards in adolescents with BD or developmental (i.e., age) associations with activation of these neural systems. The present study aims to address this knowledge gap. The present sample included 21 adolescents with BD and 26 healthy adolescents, ages 13 to 19. Participants completed a functional magnetic resonance imaging (fMRI) protocol using the Monetary Incentive Delay (MID) task. Behavioral performance was similar between groups. Group differences in BOLD activation during target anticipation and feedback anticipation periods of the task were examined using whole-brain analyses, as were group differences in age effects. During both target anticipation and feedback anticipation, adolescents with BD, compared to adolescents without psychopathology, exhibited decreased engagement of frontal regions involved in cognitive control (i.e., dorsolateral prefrontal cortex). Healthy adolescents exhibited age-related decreases, while adolescents with BD exhibited age-related increases, in activity of other cognitive control frontal areas (i.e., right inferior frontal gyrus), suggesting altered development in the BD group. Longitudinal research is needed to examine potentially abnormal development of cognitive control during reward pursuit in adolescent BD and whether early therapeutic interventions can prevent these potential deviations from normative development.

Naive-like Conversion Overcomes the Limited Differentiation Capacity of Induced Pluripotent Stem Cells*

PubMed Central

Honda, Arata; Hatori, Masanori; Hirose, Michiko; Honda, Chizumi; Izu, Haruna; Inoue, Kimiko; Hirasawa, Ryutaro; Matoba, Shogo; Togayachi, Sumie; Miyoshi, Hiroyuki; Ogura, Atsuo

2013-01-01

Although induced pluripotent stem (iPS) cells are indistinguishable from ES cells in their expression of pluripotent markers, their differentiation into targeted cells is often limited. Here, we examined whether the limited capacity of iPS cells to differentiate into neural lineage cells could be mitigated by improving their base-line level of pluripotency, i.e. by converting them into the so-called “naive” state. In this study, we used rabbit iPS and ES cells because of the easy availability of both cell types and their typical primed state characters. Repeated passages of the iPS cells permitted their differentiation into early neural cell types (neural stem cells, neurons, and glial astrocytes) with efficiencies similar to ES cells. However, unlike ES cells, their ability to differentiate later into neural cells (oligodendrocytes) was severely compromised. In contrast, after these iPS cells had been converted to a naive-like state, they readily differentiated into mature oligodendrocytes developing characteristic ramified branches, which could not be attained even with ES cells. These results suggest that the naive-like conversion of iPS cells might endow them with a higher differentiation capacity. PMID:23880763

Developmental trajectory of neural specialization for letter and number visual processing.

PubMed

Park, Joonkoo; van den Berg, Berry; Chiang, Crystal; Woldorff, Marty G; Brannon, Elizabeth M

2018-05-01

Adult neuroimaging studies have demonstrated dissociable neural activation patterns in the visual cortex in response to letters (Latin alphabet) and numbers (Arabic numerals), which suggest a strong experiential influence of reading and mathematics on the human visual system. Here, developmental trajectories in the event-related potential (ERP) patterns evoked by visual processing of letters, numbers, and false fonts were examined in four different age groups (7-, 10-, 15-year-olds, and young adults). The 15-year-olds and adults showed greater neural sensitivity to letters over numbers in the left visual cortex and the reverse pattern in the right visual cortex, extending previous findings in adults to teenagers. In marked contrast, 7- and 10-year-olds did not show this dissociable neural pattern. Furthermore, the contrast of familiar stimuli (letters or numbers) versus unfamiliar ones (false fonts) showed stark ERP differences between the younger (7- and 10-year-olds) and the older (15-year-olds and adults) participants. These results suggest that both coarse (familiar versus unfamiliar) and fine (letters versus numbers) tuning for letters and numbers continue throughout childhood and early adolescence, demonstrating a profound impact of uniquely human cultural inventions on visual cognition and its development. © 2017 John Wiley & Sons Ltd.

Infant Neural Sensitivity to Dynamic Eye Gaze Relates to Quality of Parent-Infant Interaction at 7-Months in Infants at Risk for Autism

ERIC Educational Resources Information Center

Elsabbagh, Mayada; Bruno, Ruth; Wan, Ming Wai; Charman, Tony; Johnson, Mark H.; Green, Jonathan

2015-01-01

Links between brain function measures and quality of parent-child interactions within the early developmental period have been investigated in typical and atypical development. We examined such links in a group of 104 infants with and without a family history for autism in the first year of life. Our findings suggest robust associations between…

Spatiotemporal characteristics and vascular sources of neural-specific and -nonspecific fMRI signals at submillimeter columnar resolution

PubMed Central

Moon, Chan Hong; Fukuda, Mitsuhiro; Kim, Seong-Gi

2012-01-01

The neural specificity of hemodynamic-based functional magnetic resonance imaging (fMRI) signals are dependent on both the vascular regulation and the sensitivity of the applied fMRI technique to different types and sizes of blood vessels. In order to examine the specificity of MRI-detectable hemodynamic responses, submillimeter blood oxygenation-level dependent (BOLD) and cerebral blood volume (CBV) fMRI studies were performed in a well-established cat orientation column model at 9.4 Tesla. Neural-nonspecific and -specific signals were separated by comparing the fMRI responses of orthogonal orientation stimuli. The BOLD response was dominantly neural-nonspecific, mostly originating from pial and intracortical emerging veins, and thus was highly correlated with baseline blood volume. Uneven baseline CBV may displace or distort small functional domains in high-resolution BOLD maps. The CBV response in the parenchyma exhibited dual spatiotemporal characteristics, a fast and early neural-nonspecific response (with 4.3-s time constant) and a slightly slower and delayed neural-specific response (with 9.4-s time constant). The nonspecific CBV signal originates from early-responding arteries and arterioles, while the specific CBV response, which is not correlated with baseline blood volume, arises from late-responding microvessels including small pre-capillary arterioles and capillaries. Our data indicate that although the neural specificity of CBV fMRI signals is dependent on stimulation duration, high-resolution functional maps can be obtained from steady-state CBV studies. PMID:22960251

Variation in social relationships relates to song preferences and EGR1 expression in a female songbird.

PubMed

Schubloom, Hannah E; Woolley, Sarah C

2016-09-01

Social experiences can profoundly shape social behavior and the underlying neural circuits. Across species, the formation of enduring social relationships is associated with both neural and behavioral changes. However, it remains unclear how longer-term relationships between individuals influence brain and behavior. Here, we investigated how variation in social relationships relates to variation in female preferences for and neural responses to song in a pair-bonding songbird. We assessed variation in the interactions between individuals in male-female zebra finch pairs and found that female preferences for their mate's song were correlated with the degree of affiliation and amount of socially modulated singing, but not with the frequency of aggressive interactions. Moreover, variation in measures of pair quality and preference correlated with variation in the song-induced expression of EGR1, an immediate early gene related to neural activity and plasticity, in brain regions important for auditory processing and social behavior. For example, females with weaker preferences for their mate's song had greater EGR1 expression in the nucleus Taeniae, the avian homologue of the mammalian medial amygdala, in response to playback of their mate's courtship song. Our data indicate that the quality of social interactions within pairs relates to variation in song preferences and neural responses to ethologically relevant stimuli and lend insight into neural circuits sensitive to social information. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1029-1040, 2016. © 2016 Wiley Periodicals, Inc.

Atypical EEG power correlates with indiscriminately friendly behavior in internationally adopted children.

PubMed

Tarullo, Amanda R; Garvin, Melissa C; Gunnar, Megan R

2011-03-01

While effects of institutional care on behavioral development have been studied extensively, effects on neural systems underlying these socioemotional and attention deficits are only beginning to be examined. The current study assessed electroencephalogram (EEG) power in 18-month-old internationally adopted, postinstitutionalized children (n = 37) and comparison groups of nonadopted children (n = 47) and children internationally adopted from foster care (n = 39). For their age, postinstitutionalized children had an atypical EEG power distribution, with relative power concentrated in lower frequency bands compared with nonadopted children. Both internationally adopted groups had lower absolute alpha power than nonadopted children. EEG power was not related to growth at adoption or to global cognitive ability. Atypical EEG power distribution at 18 months predicted indiscriminate friendliness and poorer inhibitory control at 36 months. Both postinstitutionalized and foster care children were more likely than nonadopted children to exhibit indiscriminate friendliness. Results are consistent with a cortical hypoactivation model of the effects of early deprivation on neural development and provide initial evidence associating this atypical EEG pattern with indiscriminate friendliness. Outcomes observed in the foster care children raise questions about the specificity of institutional rearing as a risk factor and emphasize the need for broader consideration of the effects of early deprivation and disruptions in care. PsycINFO Database Record (c) 2011 APA, all rights reserved.

Detection of apnea using a short-window FFT technique and an artificial neural network

NASA Astrophysics Data System (ADS)

Waldemark, Karina E.; Agehed, Kenneth I.; Lindblad, Thomas; Waldemark, Joakim T. A.

1998-03-01

Sleep apnea is characterized by frequent prolonged interruptions of breathing during sleep. This syndrome causes severe sleep disorders and is often responsible for development of other diseases such as heart problems, high blood pressure and daytime fatigue, etc. After diagnosis, sleep apnea is often successfully treated by applying positive air pressure (CPAP) to the mouth and nose. Although effective, the (CPAP) equipment takes up a lot of space and the connected mask causes a lot of inconvenience for the patients. This raised interest in developing new techniques for treatment of sleep apnea syndrome. Several studies have indicated that electrical stimulation of the hypoglossal nerve and muscle in the tongue may be a useful method for treating patients with severe sleep apnea. In order to be able to successfully prevent the occurrence of apnea it is necessary to have some technique for early and fast on-line detection or prediction of the apnea events. This paper suggests using measurements of respiratory airflow (mouth temperature). The signal processing for this task includes the use of a short window FFT technique and uses an artificial back propagation neural net to model or predict the occurrence of apneas. The results show that early detection of respiratory interruption is possible and that the delay time for this is small.

Atypical EEG Power Correlates With Indiscriminately Friendly Behavior in Internationally Adopted Children

PubMed Central

Tarullo, Amanda R.; Garvin, Melissa C.; Gunnar, Megan R.

2012-01-01

While effects of institutional care on behavioral development have been studied extensively, effects on neural systems underlying these socioemotional and attention deficits are only beginning to be examined. The current study assessed electroencephalogram (EEG) power in 18-month-old internationally adopted, post-institutionalized children (n = 37) and comparison groups of non-adopted children (n = 47) and children internationally adopted from foster care (n = 39). For their age, post-institutionalized children had an atypical EEG power distribution, with relative power concentrated in lower frequency bands compared to non-adopted children. Both internationally adopted groups had lower absolute alpha power than non-adopted children. EEG power was not related to growth at adoption or to global cognitive ability. Atypical EEG power distribution at 18 months predicted indiscriminate friendliness and poorer inhibitory control at 36 months. Both post-institutionalized and foster care children were more likely than non-adopted children to exhibit indiscriminate friendliness. Results are consistent with a cortical hypoactivation model of the effects of early deprivation on neural development and provide initial evidence associating this atypical EEG pattern with indiscriminate friendliness. Outcomes observed in the foster care children raise questions about the specificity of institutional rearing as a risk factor and emphasize the need for broader consideration of the effects of early deprivation and disruptions in care. PMID:21171750

Mirror-image duplication of the primary axis and heart in Xenopus embryos by the overexpression of Msx-1 gene.

PubMed

Chen, Y; Solursh, M

1995-10-01

The Msx-1 gene (formerly known as Hox-7) is a member of a discrete subclass of homeobox-containing genes. Examination of the expression pattern of Msx-1 in murine and avian embryos suggests that this gene may be involved in the regionalization of the medio-lateral axis during earlier development. We have examined the possible functions of Xenopus Msx-1 during early Xenopus embryonic development by overexpression of the Msx-1 gene. Overexpression of Msx-1 causes a left-right mirror-image duplication of primary axial structures, including notochord, neural tube, somites, suckers, and foregut. The embryonic developing heart is also mirror-image duplicated, including looping directions and polarity. These results indicate that Msx-1 may be involved in the mesoderm formation as well as left-right patterning in the early Xenopus embryonic development.

Glycoconjugates reveal diversity of human neural stem cells (hNSCs) derived from human induced pluripotent stem cells (hiPSCs).

PubMed

Kandasamy, Majury; Roll, Lars; Langenstroth, Daniel; Brüstle, Oliver; Faissner, Andreas

2017-06-01

Neural stem cells (NSCs) have the ability to self-renew and to differentiate into various cell types of the central nervous system. This potential can be recapitulated by human induced pluripotent stem cells (hiPSCs) in vitro. The differentiation capacity of hiPSCs is characterized by several stages with distinct morphologies and the expression of various marker molecules. We used the monoclonal antibodies (mAbs) 487 LeX , 5750 LeX and 473HD to analyze the expression pattern of particular carbohydrate motifs as potential markers at six differentiation stages of hiPSCs. Mouse ESCs were used as a comparison. At the pluripotent stage, 487 LeX -, 5750 LeX - and 473HD-related glycans were differently expressed. Later, cells of the three germ layers in embryoid bodies (hEBs) and, even after neuralization of hEBs, subpopulations of cells were labeled with these surface antibodies. At the human rosette-stage of NSCs (hR-NSC), LeX- and 473HD-related epitopes showed antibody-specific expression patterns. We also found evidence that these surface antibodies could be used to distinguish the hR-NSCs from the hSR-NSCs stages. Characterization of hNSCs FGF-2/EGF derived from hSR-NSCs revealed that both LeX antibodies and the 473HD antibody labeled subpopulations of hNSCs FGF-2/EGF . Finally, we identified potential LeX carrier molecules that were spatiotemporally regulated in early and late stages of differentiation. Our study provides new insights into the regulation of glycoconjugates during early human stem cell development. The mAbs 487 LeX , 5750 LeX and 473HD are promising tools for identifying distinct stages during neural differentiation.

[Injuries of the cervical spine in patients with ankylosing spondylitis].

PubMed

Vaverka, M; Hrabálek, L

2001-01-01

A brittle and rigid, osteoporotic and injury prone "bamboo" spine which develops as a result of transformation of the normal spine in the final stage of Bekhterev's disease contains normal neural elements. Unstable fractures occur frequently even after a minimal injury and the morbidity and mortality is significantly higher than in the group of routine injuries of the cervical, spine, in particular as a result of pulmonary complications. Diagnosis of the fracture based on simple X-ray pictures is difficult, CT examination is essential. The authors present an account on their experience with three patients. They draw attention to problems of skeletal traction when the spinal axis is altered by disease and to risks associated with semiconservative treatment. The authors therefore recommend traction with a minimal load and with subsequent early decompression and stabilization by a combined anterior and posterior approach in a single session. By this approach secondary affection of neural structures in unstable fractures can be prevented, and early rehabilitation with verticalization without restriction of respiratory excursions by an orthesis then significantly reduces the risk of pulmonary complications.

Harsh Parenting and Fearfulness in Toddlerhood Interact to Predict Amplitudes of Preschool Error-Related Negativity

PubMed Central

Brooker, Rebecca J.; Buss, Kristin A.

2014-01-01

Temperamentally fearful children are at increased risk for the development of anxiety problems relative to less-fearful children. This risk is even greater when early environments include high levels of harsh parenting behaviors. However, the mechanisms by which harsh parenting may impact fearful children’s risk for anxiety problems are largely unknown. Recent neuroscience work has suggested that punishment is associated with exaggerated error-related negativity (ERN), an event-related potential linked to performance monitoring, even after the threat of punishment is removed. In the current study, we examined the possibility that harsh parenting interacts with fearfulness, impacting anxiety risk via neural processes of performance monitoring. We found that greater fearfulness and harsher parenting at 2 years of age predicted greater fearfulness and greater ERN amplitudes at age 4. Supporting the role of cognitive processes in this association, greater fearfulness and harsher parenting also predicted less efficient neural processing during preschool. This study provides initial evidence that performance monitoring may be a candidate process by which early parenting interacts with fearfulness to predict risk for anxiety problems. PMID:24721466

Diabetes and apoptosis: neural crest cells and neural tube.

PubMed

Chappell, James H; Wang, Xiao Dan; Loeken, Mary R

2009-12-01

Birth defects resulting from diabetic pregnancy are associated with apoptosis of a critical mass of progenitor cells early during the formation of the affected organ(s). Insufficient expression of genes that regulate viability of the progenitor cells is responsible for the apoptosis. In particular, maternal diabetes inhibits expression of a gene, Pax3, that encodes a transcription factor which is expressed in neural crest and neuroepithelial cells. As a result of insufficient Pax3, cardiac neural crest and neuroepithelial cells undergo apoptosis by a process dependent on the p53 tumor suppressor protein. This, then provides a cellular explanation for the cardiac outflow tract and neural tube and defects induced by diabetic pregnancy.

Diabetes and apoptosis: neural crest cells and neural tube

PubMed Central

Chappell, James H.; Dan Wang, Xiao

2016-01-01

Birth defects resulting from diabetic pregnancy are associated with apoptosis of a critical mass of progenitor cells early during the formation of the affected organ(s). Insufficient expression of genes that regulate viability of the progenitor cells is responsible for the apoptosis. In particular, maternal diabetes inhibits expression of a gene, Pax3, that encodes a transcription factor which is expressed in neural crest and neuroepithelial cells. As a result of insufficient Pax3, cardiac neural crest and neuroepithelial cells undergo apoptosis by a process dependent on the p53 tumor suppressor protein. This, then provides a cellular explanation for the cardiac outflow tract and neural tube and defects induced by diabetic pregnancy. PMID:19333760

Lateralization of ERPs to speech and handedness in the early development of Autism Spectrum Disorder.

PubMed

Finch, Kayla H; Seery, Anne M; Talbott, Meagan R; Nelson, Charles A; Tager-Flusberg, Helen

2017-01-01

Language is a highly lateralized function, with typically developing individuals showing left hemispheric specialization. Individuals with autism spectrum disorder (ASD) often show reduced or reversed hemispheric lateralization in response to language. However, it is unclear when this difference emerges and whether or not it can serve as an early ASD biomarker. Additionally, atypical language lateralization is not specific to ASD as it is also seen more frequently in individuals with mixed- and left-handedness. Here, we examined early asymmetry patterns measured through neural responses to speech sounds at 12 months and behavioral observations of handedness at 36 months in children with and without ASD. Three different groups of children participated in the study: low-risk controls (LRC), high risk for ASD (HRA; infants with older sibling with ASD) without ASD, and HRA infants who later receive a diagnosis of ASD (ASD). Event-related potentials (ERPs) to speech sounds were recorded at 12 months. Utilizing a novel observational approach, handedness was measured by hand preference on a variety of behaviors at 36 months. At 12 months, lateralization patterns of ERPs to speech stimuli differed across the groups with the ASD group showing reversed lateralization compared to the LRC group. At 36 months, factor analysis of behavioral observations of hand preferences indicated a one-factor model with medium to high factor loadings. A composite handedness score was derived; no group differences were observed. There was no association between lateralization to speech at 12 months and handedness at 36 months in the LRC and HRA groups. However, children with ASD did show an association such that infants with lateralization patterns more similar to the LRC group at 12 months were stronger right-handers at 36 months. These results highlight early developmental patterns that might be specific to ASD, including a potential early biomarker of reversed lateralization to speech stimuli at 12 months, and a relation between behavioral and neural asymmetries. Future investigations of early asymmetry patterns, especially atypical hemispheric specialization, may be informative in the early identification of ASD.

Gap-Junctional communication between developing Drosophila muscles is essential for their normal development.

PubMed

Todman, M G; Baines, R A; Stebbings, L A; Davies, J A; Bacon, J P

1999-01-01

Recent experiments have demonstrated that a family of proteins, known as the innexins, are structural components of invertebrate gap junctions. The shaking-B (shak-B) locus of Drosophila encodes two members of this emerging family, Shak-B(lethal) and Shak-B(neural). This study focuses on the role of Shak-B gap junctions in the development of embryonic and larval muscle. During embryogenesis, shak-B transcripts are expressed in a subset of the somatic muscles; expression is strong in ventral oblique muscles (VO4-6) but only weak in ventral longitudinals (VL3 and 4). Carboxyfluorescein injected into VO4 of wild-type early stage 16 embryos spreads, via gap junctions, to label adjacent muscles, including VL3 and 4. In shak-B2 embryos (in which the shak-B(neural) function is disrupted), dye injected into VO4 fails to spread into other muscles. In the first instar larva, when dye coupling between muscles is no longer present, another effect of the shak-B2 mutation is revealed by whole-cell voltage clamp. In a calcium-free saline, only two voltage-activated potassium currents are present in wild-type muscles; a fast IA and a slow IK current. In shak-B2 larvae, these two currents are significantly reduced in magnitude in VO4 and 5, but remain normal in VL3. Expression of shak-B(neural) in a shak-B2 background fully rescues both dye coupling in embryonic muscle and whole-cell currents in first instar VO4 and 5. Our observations show that Shak-B(neural) is one of a set of embryonic gap-junction proteins, and that it is required for the normal temporal development of potassium currents in some larval muscles.

Early-onset Alzheimer's Disease Phenotypes: Neuropsychology and Neural Networks

ClinicalTrials.gov

2017-05-11

Alzheimer Disease, Early Onset; Alzheimer Disease; Alzheimer Disease, Late Onset; Dementia, Alzheimer Type; Logopenic Progressive Aphasia; Primary Progressive Aphasia; Visuospatial/Perceptual Abilities; Posterior Cortical Atrophy; Executive Dysfunction; Corticobasal Degeneration; Ideomotor Apraxia

Brief Report: Robo1 Regulates the Migration of Human Subventricular Zone Neural Progenitor Cells During Development.

PubMed

Guerrero-Cazares, Hugo; Lavell, Emily; Chen, Linda; Schiapparelli, Paula; Lara-Velazquez, Montserrat; Capilla-Gonzalez, Vivian; Clements, Anna Christina; Drummond, Gabrielle; Noiman, Liron; Thaler, Katrina; Burke, Anne; Quiñones-Hinojosa, Alfredo

2017-07-01

Human neural progenitor cell (NPC) migration within the subventricular zone (SVZ) of the lateral ganglionic eminence is an active process throughout early brain development. The migration of human NPCs from the SVZ to the olfactory bulb during fetal stages resembles what occurs in adult rodents. As the human brain develops during infancy, this migratory stream is drastically reduced in cell number and becomes barely evident in adults. The mechanisms regulating human NPC migration are unknown. The Slit-Robo signaling pathway has been defined as a chemorepulsive cue involved in axon guidance and neuroblast migration in rodents. Slit and Robo proteins expressed in the rodent brain help guide neuroblast migration from the SVZ through the rostral migratory stream to the olfactory bulb. Here, we present the first study on the role that Slit and Robo proteins play in human-derived fetal neural progenitor cell migration (hfNPC). We describe that Robo1 and Robo2 isoforms are expressed in the human fetal SVZ. Furthermore, we demonstrate that Slit2 is able to induce a chemorepellent effect on the migration of hfNPCs derived from the human fetal SVZ. In addition, when Robo1 expression is inhibited, hfNPCs are unable to migrate to the olfactory bulb of mice when injected in the anterior SVZ. Our findings indicate that the migration of human NPCs from the SVZ is partially regulated by the Slit-Robo axis. This pathway could be regulated to direct the migration of NPCs in human endogenous neural cell therapy. Stem Cells 2017;35:1860-1865. © 2017 AlphaMed Press.

Alterations of parenchymal microstructure, neuronal connectivity and cerebrovascular resistance at adolescence following mild to moderate traumatic brain injury in early development.

PubMed

Parent, Maxime; Li, Ying; Santhakumar, Vijayalakshmi; Hyder, Fahmeed; Sanganahalli, Basavaraju G; Kannurpatti, Sridhar

2018-06-01

TBI is a leading cause of morbidity in children. To investigate outcome of early developmental TBI during adolescence, a rat model of fluid percussion injury was developed, where previous work reported deficits in sensorimotor behavior and cortical blood flow at adolescence. 1 Based on the non-localized outcome, we hypothesized that multiple neurophysiological components of brain function, namely neuronal connectivity, synapse/axonal microstructural integrity and neurovascular function are altered and magnetic resonance imaging (MRI) methods could be used to determine regional alterations. Adolescent outcomes of developmental TBI were studied 2-months after injury, using functional MRI (fMRI) and Diffusion Tensor Imaging (DTI). fMRI based resting state functional connectivity (RSFC), representing neural connectivity, was significantly altered between sham and TBI. RSFC strength decreased in the cortex, hippocampus and thalamus accompanied by decrease in the spatial extent of their corresponding RSFC networks and inter-hemispheric asymmetry. Cerebrovascular reactivity to arterial CO2 changes diminished after TBI across both hemispheres, with a more pronounced decrease in the ipsilateral hippocampus, thalamus and motor cortex. DTI measures of fractional anisotropy (FA) and apparent diffusion coefficient (ADC), reporting on axonal and microstructural integrity of the brain, indicated similar inter-hemispheric asymmetry, with highest change in the ipsilateral hippocampus and regions adjoining the ipsilateral thalamus, hypothalamus and amygdala. TBI-induced corpus callosal microstructural alterations indicated measurable changes in inter-hemispheric structural connectivity. Hippocampus, thalamus and select cortical regions were most consistently affected in multiple imaging markers. The multi-modal MRI results demonstrate cortical and subcortical alterations in neural connectivity, cerebrovascular resistance and parenchymal microstructure in the adolescent brain, indicating the highly diffuse and persistent nature of the lateral fluid percussion TBI early in development.

Behavioral and neural plasticity caused by early social experiences: the case of the honeybee

PubMed Central

Arenas, Andrés; Ramírez, Gabriela P.; Balbuena, María Sol; Farina, Walter M.

2013-01-01

Cognitive experiences during the early stages of life play an important role in shaping future behavior. Behavioral and neural long-term changes after early sensory and associative experiences have been recently reported in the honeybee. This invertebrate is an excellent model for assessing the role of precocious experiences on later behavior due to its extraordinarily tuned division of labor based on age polyethism. These studies are mainly focused on the role and importance of experiences occurred during the first days of the adult lifespan, their impact on foraging decisions, and their contribution to coordinate food gathering. Odor-rewarded experiences during the first days of honeybee adulthood alter the responsiveness to sucrose, making young hive bees more sensitive to assess gustatory features about the nectar brought back to the hive and affecting the dynamic of the food transfers and the propagation of food-related information within the colony. Early olfactory experiences lead to stable and long-term associative memories that can be successfully recalled after many days, even at foraging ages. Also they improve memorizing of new associative learning events later in life. The establishment of early memories promotes stable reorganization of the olfactory circuits inducing structural and functional changes in the antennal lobe (AL). Early rewarded experiences have relevant consequences at the social level too, biasing dance and trophallaxis partner choice and affecting recruitment. Here, we revised recent results in bees' physiology, behavior, and sociobiology to depict how the early experiences affect their cognition abilities and neural-related circuits. PMID:23986708

Neural processing of high and low spatial frequency information in faces changes across development: qualitative changes in face processing during adolescence.

PubMed

Peters, Judith C; Vlamings, Petra; Kemner, Chantal

2013-05-01

Face perception in adults depends on skilled processing of interattribute distances ('configural' processing), which is disrupted for faces presented in inverted orientation (face inversion effect or FIE). Children are not proficient in configural processing, and this might relate to an underlying immaturity to use facial information in low spatial frequency (SF) ranges, which capture the coarse information needed for configural processing. We hypothesized that during adolescence a shift from use of high to low SF information takes place. Therefore, we studied the influence of SF content on neural face processing in groups of children (9-10 years), adolescents (14-15 years) and young adults (21-29 years) by measuring event-related potentials (ERPs) to upright and inverted faces which varied in SF content. Results revealed that children show a neural FIE in early processing stages (i.e. P1; generated in early visual areas), suggesting a superficial, global facial analysis. In contrast, ERPs of adults revealed an FIE at later processing stages (i.e. N170; generated in face-selective, higher visual areas). Interestingly, adolescents showed FIEs in both processing stages, suggesting a hybrid developmental stage. Furthermore, adolescents and adults showed FIEs for stimuli containing low SF information, whereas such effects were driven by both low and high SF information in children. These results indicate that face processing has a protracted maturational course into adolescence, and is dependent on changes in SF processing. During adolescence, sensitivity to configural cues is developed, which aids the fast and holistic processing that is so special for faces. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Economic, neurobiological, and behavioral perspectives on building America’s future workforce

PubMed Central

Knudsen, Eric I.; Heckman, James J.; Cameron, Judy L.; Shonkoff, Jack P.

2006-01-01

A growing proportion of the U.S. workforce will have been raised in disadvantaged environments that are associated with relatively high proportions of individuals with diminished cognitive and social skills. A cross-disciplinary examination of research in economics, developmental psychology, and neurobiology reveals a striking convergence on a set of common principles that account for the potent effects of early environment on the capacity for human skill development. Central to these principles are the findings that early experiences have a uniquely powerful influence on the development of cognitive and social skills and on brain architecture and neurochemistry, that both skill development and brain maturation are hierarchical processes in which higher level functions depend on, and build on, lower level functions, and that the capacity for change in the foundations of human skill development and neural circuitry is highest earlier in life and decreases over time. These findings lead to the conclusion that the most efficient strategy for strengthening the future workforce, both economically and neurobiologically, and improving its quality of life is to invest in the environments of disadvantaged children during the early childhood years. PMID:16801553

Commentary: Elucidating the Neural Correlates of Early Childhood Memory

ERIC Educational Resources Information Center

Mullally, Sinead L.

2015-01-01

Both episodic memory and the key neural structure believed to support it, namely the hippocampus, are believed to undergo protracted periods of postnatal developmental. Critically however, the hippocampus is comprised of distinct subfields and circuits, and these circuits appear to mature at different rates (Lavenex and Banta Lavenex, 2013).…

Onset age of L2 acquisition influences language network in early and late Cantonese-Mandarin bilinguals.

PubMed

Liu, Xiaojin; Tu, Liu; Wang, Junjing; Jiang, Bo; Gao, Wei; Pan, Ximin; Li, Meng; Zhong, Miao; Zhu, Zhenzhen; Niu, Meiqi; Li, Yanyan; Zhao, Ling; Chen, Xiaoxi; Liu, Chang; Lu, Zhi; Huang, Ruiwang

2017-11-01

Early second language (L2) experience influences the neural organization of L2 in neuro-plastic terms. Previous studies tried to reveal these plastic effects of age of second language acquisition (AoA-L2) and proficiency-level in L2 (PL-L2) on the neural basis of language processing in bilinguals. Although different activation patterns have been observed during language processing in early and late bilinguals by task-fMRI, few studies reported the effect of AoA-L2 and high PL-L2 on language network at resting state. In this study, we acquired resting-state fMRI (R-fMRI) data from 10 Cantonese (L1)-Mandarin (L2) early bilinguals (acquired L2: 3years old) and 11 late bilinguals (acquired L2: 6years old), and analyzed their topological properties of language networks after controlling the language daily exposure and usage as well as PL in L1 and L2. We found that early bilinguals had significantly a higher clustering coefficient, global and local efficiency, but significantly lower characteristic path length compared to late bilinguals. Modular analysis indicated that compared to late bilinguals, early bilinguals showed significantly stronger intra-modular functional connectivity in the semantic and phonetic modules, stronger inter-modular functional connectivity between the semantic and phonetic modules as well as between the phonetic and syntactic modules. Differences in global and local parameters may reflect different patterns of neuro-plasticity respectively for early and late bilinguals. These results suggested that different L2 experience influences topological properties of language network, even if late bilinguals achieve high PL-L2. Our findings may provide a new perspective of neural mechanisms related to early and late bilinguals. Copyright © 2017 Elsevier Inc. All rights reserved.

A failure of left temporal cortex to specialize for language is an early emerging and fundamental property of autism

PubMed Central

Pierce, Karen; Courchesne, Eric

2012-01-01

Failure to develop normal language comprehension is an early warning sign of autism, but the neural mechanisms underlying this signature deficit are unknown. This is because of an almost complete absence of functional studies of the autistic brain during early development. Using functional magnetic resonance imaging, we previously observed a trend for abnormally lateralized temporal responses to language (i.e. greater activation on the right, rather than the expected left) in a small sample (n = 12) of sleeping 2–3 year olds with autism in contrast to typically developing children, a finding also reported in autistic adults and adolescents. It was unclear, however, if findings of atypical laterality would be observed in a larger sample, and at even earlier ages in autism, such as around the first birthday. Answers to these questions would provide the foundation for understanding how neurofunctional defects of autism unfold, and provide a foundation for studies using patterns of brain activation as a functional early biomarker of autism. To begin to examine these issues, a prospective, cross-sectional design was used in which brain activity was measured in a large sample of toddlers (n = 80) during the presentation of a bedtime story during natural sleep. Forty toddlers with autism spectrum disorder and 40 typically developing toddlers ranging in age between 12–48 months participated. Any toddler with autism who participated in the imaging experiment prior to final diagnosis was tracked and diagnoses confirmed at a later age. Results indicated that at-risk toddlers later diagnosed as autistic display deficient left hemisphere response to speech sounds and have abnormally right-lateralized temporal cortex response to language; this defect worsens with age, becoming most severe in autistic 3- and 4-year-olds. Typically developing children show opposite developmental trends with a tendency towards greater temporal cortex response with increasing age and maintenance of left-lateralized activation with age. We have now demonstrated lateralized abnormalities of temporal cortex processing of language in autism across two separate samples, including a large sample of young infants who later are diagnosed with autism, suggesting that this pattern may reflect a fundamental early neural developmental pathology in autism. PMID:22350062

Neural Predictors of Visuomotor Adaptation Rate and Multi-Day Savings

NASA Technical Reports Server (NTRS)

Cassady, Kaitlin; Ruitenberg, Marit; Koppelmans, Vincent; Reuter-Lorenz, Patricia; De Dios, Yiri; Gadd, Nichole; Wood, Scott; Riascos Castenada, Roy; Kofman, Igor; Bloomberg, Jacob;

Changes of neural markers expression during late neurogenic differentiation of human adipose-derived stem cells

PubMed Central

Razavi, Shahnaz; Khosravizadeh, Zahra; Bahramian, Hamid; Kazemi, Mohammad

2015-01-01

Background: Different studies have been done to obtain sufficient number of neural cells for treatment of neurodegenerative diseases, spinal cord, and traumatic brain injury because neural stem cells are limited in central nerves system. Recently, several studies have shown that adipose-derived stem cells (ADSCs) are the appropriate source of multipotent stem cells. Furthermore, these cells are found in large quantities. The aim of this study was an assessment of proliferation and potential of neurogenic differentiation of ADSCs with passing time. Materials and Methods: Neurosphere formation was used for neural induction in isolated human ADSCs (hADSCs). The rate of proliferation was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and potential of neural differentiation of induced hADSCs was evaluated by immunocytochemical and real-time reverse transcription polymerase chain reaction analysis after 10 and 14 days post-induction. Results: The rate of proliferation of induced hADSCs increased after 14 days while the expression of nestin, glial fibrillary acidic protein, and microtubule-associated protein 2 was decreased with passing time during neurogenic differentiation. Conclusion: These findings showed that the proliferation of induced cells increased with passing time, but in early neurogenic differentiation of hADSCs, neural expression was higher than late of differentiation. Thus, using of induced cells in early differentiation may be suggested for in vivo application. PMID:26605238

Can very early music interventions promote at-risk infants' development?

PubMed

Virtala, Paula; Partanen, Eino

2018-04-30

Music and musical activities are often a natural part of parenting. As accumulating evidence shows, music can promote auditory and language development in infancy and early childhood. It may even help to support auditory and language skills in infants whose development is compromised by heritable conditions, like the reading deficit dyslexia, or by environmental factors, such as premature birth. For example, infants born to dyslexic parents can have atypical brain responses to speech sounds and subsequent challenges in language development. Children born very preterm, in turn, have an increased likelihood of sensory, cognitive, and motor deficits. To ameliorate these deficits, we have developed early interventions focusing on music. Preliminary results of our ongoing longitudinal studies suggest that music making and parental singing promote infants' early language development and auditory neural processing. Together with previous findings in the field, the present studies highlight the role of active, social music making in supporting auditory and language development in at-risk children and infants. Once completed, the studies will illuminate both risk and protective factors in development and offer a comprehensive model of understanding the promises of music activities in promoting positive developmental outcomes during the first years of life. © 2018 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals Inc. on behalf of The New York Academy of Sciences.

Longitudinal change in the neural bases of adolescent social self-evaluations: effects of age and pubertal development.

PubMed

Pfeifer, Jennifer H; Kahn, Lauren E; Merchant, Junaid S; Peake, Shannon J; Veroude, Kim; Masten, Carrie L; Lieberman, Matthew D; Mazziotta, John C; Dapretto, Mirella

2013-04-24

Self-evaluations undergo significant transformation during early adolescence, developing in parallel with the heightened complexity of teenagers' social worlds. Intuitive theories of adolescent development, based in part on animal work, suggest that puberty is associated with neural-level changes that facilitate a "social reorientation" (Nelson et al., 2005). However, direct tests of this hypothesis using neuroimaging are limited in humans. This longitudinal fMRI study examined neurodevelopmental trajectories associated with puberty, self-evaluations, and the presumed social reorientation during the transition from childhood to adolescence. Participants (N = 27, mean age = 10.1 and 13.1 years at time points one and two, respectively) engaged in trait evaluations of two targets (the self and a familiar fictional other), across two domains of competence (social and academic). Responses in ventromedial PFC increased with both age and pubertal development during self-evaluations in the social domain, but not in the academic domain. These results suggest that changes in social self-evaluations are intimately connected with biology, not just peer contexts, and provide important empirical support for the relationship between neurodevelopment, puberty, and social functioning.

Functional mapping of the neural circuitry of rat maternal motivation: effects of site-specific transient neural inactivation

PubMed Central

Pereira, Mariana; Morrell, Joan I.

2011-01-01

The present review focuses on recent studies from our laboratory examining the neural circuitry subserving rat maternal motivation across postpartum. We employed a site-specific neural inactivation method by infusion of bupivacaine to map the maternal motivation circuitry using two complementary behavioral approaches: unconditioned maternal responsiveness and choice of pup- over cocaine-conditioned incentives in a concurrent pup/cocaine choice conditioned place preference task. Our findings revealed that during the early postpartum period, distinct brain structures, including the medial preoptic area, ventral tegmental area and medial prefrontal cortex infralimbic and anterior cingulate subregions, contribute a pup-specific bias to the motivational circuitry. As the postpartum period progresses and the pups grow older, our findings further revealed that maternal responsiveness becomes progressively less dependent on medial preoptic area and medial prefrontal cortex infralimbic activity, and more distributed in the maternal circuitry, such that additional network components, including the medial prefrontal cortex prelimbic subregion, are recruited with maternal experience, and contribute to the expression of late postpartum maternal behavior. Collectively, our findings provide strong evidence that the remarkable ability of postpartum females to successfully care for their developing infants is subserved by a distributed neural network that carries out efficient and dynamic processing of complex, constantly changing incoming environmental and pup-related stimuli, ultimately allowing the progression of appropriate expression and waning of maternal responsiveness across the postpartum period. PMID:21815954

UArizona at the CLEF eRisk 2017 Pilot Task: Linear and Recurrent Models for Early Depression Detection

PubMed Central

Sadeque, Farig; Xu, Dongfang; Bethard, Steven

2017-01-01

The 2017 CLEF eRisk pilot task focuses on automatically detecting depression as early as possible from a users’ posts to Reddit. In this paper we present the techniques employed for the University of Arizona team’s participation in this early risk detection shared task. We leveraged external information beyond the small training set, including a preexisting depression lexicon and concepts from the Unified Medical Language System as features. For prediction, we used both sequential (recurrent neural network) and non-sequential (support vector machine) models. Our models perform decently on the test data, and the recurrent neural models perform better than the non-sequential support vector machines while using the same feature sets. PMID:29075167

Monoamine Oxidases Regulate Telencephalic Neural Progenitors in Late Embryonic and Early Postnatal Development

PubMed Central

Cheng, Aiwu; Scott, Anna L.; Ladenheim, Bruce; Chen, Kevin; Ouyang, Xin; Lathia, Justin D.; Mughal, Mohamed; Cadet, Jean Lud; Mattson, Mark P.; Shih, Jean C.

2010-01-01

Monoamine neurotransmitters play major roles in regulating a range of brain functions in adults and increasing evidence suggests roles for monoamines in brain development. Here we show that mice lacking the monoamine metabolic enzymes MAO A and MAO B (MAO AB-deficient mice) exhibit diminished proliferation of neural stem cells (NSC) in the developing telencephalon beginning in late gestation [embryonic day (E) 17.5], a deficit that persists in neonatal and adult mice. These mice showed significantly increased monoamine levels and anxiety-like behaviors as adults. Assessments of markers of intermediate progenitor cells (IPC) and mitosis showed that NSC in the subventricular zone (SVZ), but not in the ventricular zone, are reduced in MAO AB-deficient mice. A developmental time course of monoamines in frontal cortical tissues revealed increased serotonin levels as early as E14.5, and a further large increase was found between E17.5 and postnatal day 2. Administration of an inhibitor of serotonin synthesis (parachlorophenylalanine) between E14.5 and E19.5 restored the IPC numbers and SVZ thickness, suggesting the role of serotonin in the suppression of IPC proliferation. Studies of neurosphere cultures prepared from the telencephalon at different embryonic and postnatal ages showed that serotonin stimulates proliferation in wild-type, but not in MAO AB-deficient, NSC. Together, these results suggest that a MAO-dependent long-lasting alteration in the proliferation capacity of NSC occurs late in embryonic development and is mediated by serotonin. Our findings reveal novel roles for MAOs and serotonin in the regulation of IPC proliferation in the developing brain. PMID:20702706

Tissue Specific Roles for the Ribosome Biogenesis Factor Wdr43 in Zebrafish Development

PubMed Central

Zhao, Chengtian; Andreeva, Viktoria; Gibert, Yann; LaBonty, Melissa; Lattanzi, Victoria; Prabhudesai, Shubhangi; Zhou, Yi; Zon, Leonard; McCann, Kathleen L.; Baserga, Susan; Yelick, Pamela C.

2014-01-01

During vertebrate craniofacial development, neural crest cells (NCCs) contribute to most of the craniofacial pharyngeal skeleton. Defects in NCC specification, migration and differentiation resulting in malformations in the craniofacial complex are associated with human craniofacial disorders including Treacher-Collins Syndrome, caused by mutations in TCOF1. It has been hypothesized that perturbed ribosome biogenesis and resulting p53 mediated neuroepithelial apoptosis results in NCC hypoplasia in mouse Tcof1 mutants. However, the underlying mechanisms linking ribosome biogenesis and NCC development remain poorly understood. Here we report a new zebrafish mutant, fantome (fan), which harbors a point mutation and predicted premature stop codon in zebrafish wdr43, the ortholog to yeast UTP5. Although wdr43 mRNA is widely expressed during early zebrafish development, and its deficiency triggers early neural, eye, heart and pharyngeal arch defects, later defects appear fairly restricted to NCC derived craniofacial cartilages. Here we show that the C-terminus of Wdr43, which is absent in fan mutant protein, is both necessary and sufficient to mediate its nucleolar localization and protein interactions in metazoans. We demonstrate that Wdr43 functions in ribosome biogenesis, and that defects observed in fan mutants are mediated by a p53 dependent pathway. Finally, we show that proper localization of a variety of nucleolar proteins, including TCOF1, is dependent on that of WDR43. Together, our findings provide new insight into roles for Wdr43 in development, ribosome biogenesis, and also ribosomopathy-induced craniofacial phenotypes including Treacher-Collins Syndrome. PMID:24497835

Using sex differences in the developing brain to identify nodes of influence for seizure susceptibility and epileptogenesis.

PubMed

Kight, Katherine E; McCarthy, Margaret M

2014-12-01

Sexual differentiation of the developing brain organizes the neural architecture differently between males and females, and the main influence on this process is exposure to gonadal steroids during sensitive periods of prenatal and early postnatal development. Many molecular and cellular processes are influenced by steroid hormones in the developing brain, including gene expression, cell birth and death, neurite outgrowth and synaptogenesis, and synaptic activity. Perturbations in these processes can alter neuronal excitability and circuit activity, leading to increased seizure susceptibility and the promotion of pathological processes that constitute epileptogenesis. In this review, we will provide a general overview of sex differences in the early developing brain that may be relevant for altered seizure susceptibility in early life, focusing on limbic areas of the brain. Sex differences that have the potential to alter the progress of epileptogenesis are evident at molecular and cellular levels in the developing brain, and include differences in neuronal excitability, response to environmental insult, and epigenetic control of gene expression. Knowing how these processes differ between the sexes can help us understand fundamental mechanisms underlying gender differences in seizure susceptibility and epileptogenesis. Copyright © 2014 Elsevier Inc. All rights reserved.

Friction forces position the neural anlage

PubMed Central

Smutny, Michael; Ákos, Zsuzsa; Grigolon, Silvia; Shamipour, Shayan; Ruprecht, Verena; Čapek, Daniel; Behrndt, Martin; Papusheva, Ekaterina; Tada, Masazumi; Hof, Björn; Vicsek, Tamás; Salbreux, Guillaume; Heisenberg, Carl-Philipp

2017-01-01

During embryonic development, mechanical forces are essential for cellular rearrangements driving tissue morphogenesis. Here, we show that in the early zebrafish embryo, friction forces are generated at the interface between anterior axial mesoderm (prechordal plate, ppl) progenitors migrating towards the animal pole and neurectoderm progenitors moving in the opposite direction towards the vegetal pole of the embryo. These friction forces lead to global rearrangement of cells within the neurectoderm and determine the position of the neural anlage. Using a combination of experiments and simulations, we show that this process depends on hydrodynamic coupling between neurectoderm and ppl as a result of E-cadherin-mediated adhesion between those tissues. Our data thus establish the emergence of friction forces at the interface between moving tissues as a critical force-generating process shaping the embryo. PMID:28346437

Friction forces position the neural anlage.

PubMed

Smutny, Michael; Ákos, Zsuzsa; Grigolon, Silvia; Shamipour, Shayan; Ruprecht, Verena; Čapek, Daniel; Behrndt, Martin; Papusheva, Ekaterina; Tada, Masazumi; Hof, Björn; Vicsek, Tamás; Salbreux, Guillaume; Heisenberg, Carl-Philipp

2017-04-01

During embryonic development, mechanical forces are essential for cellular rearrangements driving tissue morphogenesis. Here, we show that in the early zebrafish embryo, friction forces are generated at the interface between anterior axial mesoderm (prechordal plate, ppl) progenitors migrating towards the animal pole and neurectoderm progenitors moving in the opposite direction towards the vegetal pole of the embryo. These friction forces lead to global rearrangement of cells within the neurectoderm and determine the position of the neural anlage. Using a combination of experiments and simulations, we show that this process depends on hydrodynamic coupling between neurectoderm and ppl as a result of E-cadherin-mediated adhesion between those tissues. Our data thus establish the emergence of friction forces at the interface between moving tissues as a critical force-generating process shaping the embryo.

Prenatal SSRI exposure: Effects on later child development.

PubMed

Hermansen, Tone Kristine; Melinder, Annika

2015-01-01

The aim of this review is to integrate research on the pharmacological mechanisms of selective serotonin reuptake inhibitors (SSRIs) and the following effects on fetal brain development and child cognitive function seen in children with prenatal exposure to SSRIs. As antidepressants are transferred from the mother to the fetus through the placenta, the fetus is vulnerable to alterations in neurotransmission and possibly altered neural functioning. Because of this risk, pregnant women suffering from depression are often advised to discontinue their use of antidepressants during pregnancy. Though, maternal untreated depression may also have negative consequences for the fetus and child after birth. In the present review, we find a distinction between studies of early versus late development. Studies on early cognitive development indicate no negative effects, while studies on later development report some cognitive difficulties and behavioral problems, indicating latent effects of exposure. However, the reviewed studies are not all converging, and it is not clear whether and to what extent prenatal SSRI exposure affects cognitive development.

Meninges: from protective membrane to stem cell niche

PubMed Central

Decimo, Ilaria; Fumagalli, Guido; Berton, Valeria; Krampera, Mauro; Bifari, Francesco

2012-01-01

Meninges are a three tissue membrane primarily known as coverings of the brain. More in depth studies on meningeal function and ultrastructure have recently changed the view of meninges as a merely protective membrane. Accurate evaluation of the anatomical distribution in the CNS reveals that meninges largely penetrate inside the neural tissue. Meninges enter the CNS by projecting between structures, in the stroma of choroid plexus and form the perivascular space (Virchow-Robin) of every parenchymal vessel. Thus, meninges may modulate most of the physiological and pathological events of the CNS throughout the life. Meninges are present since the very early embryonic stages of cortical development and appear to be necessary for normal corticogenesis and brain structures formation. In adulthood meninges contribute to neural tissue homeostasis by secreting several trophic factors including FGF2 and SDF-1. Recently, for the first time, we have identified the presence of a stem cell population with neural differentiation potential in meninges. In addition, we and other groups have further described the presence in meninges of injury responsive neural precursors. In this review we will give a comprehensive view of meninges and their multiple roles in the context of a functional network with the neural tissue. We will highlight the current literature on the developmental feature of meninges and their role in cortical development. Moreover, we will elucidate the anatomical distribution of the meninges and their trophic properties in adult CNS. Finally, we will emphasize recent evidences suggesting the potential role of meninges as stem cell niche harbouring endogenous precursors that can be activated by injury and are able to contribute to CNS parenchymal reaction. PMID:23671802

Knowledge synthesis with maps of neural connectivity.

PubMed

Tallis, Marcelo; Thompson, Richard; Russ, Thomas A; Burns, Gully A P C

2011-01-01

This paper describes software for neuroanatomical knowledge synthesis based on neural connectivity data. This software supports a mature methodology developed since the early 1990s. Over this time, the Swanson laboratory at USC has generated an account of the neural connectivity of the sub-structures of the hypothalamus, amygdala, septum, hippocampus, and bed nucleus of the stria terminalis. This is based on neuroanatomical data maps drawn into a standard brain atlas by experts. In earlier work, we presented an application for visualizing and comparing anatomical macro connections using the Swanson third edition atlas as a framework for accurate registration. Here we describe major improvements to the NeuARt application based on the incorporation of a knowledge representation of experimental design. We also present improvements in the interface and features of the data mapping components within a unified web-application. As a step toward developing an accurate sub-regional account of neural connectivity, we provide navigational access between the data maps and a semantic representation of area-to-area connections that they support. We do so based on an approach called "Knowledge Engineering from Experimental Design" (KEfED) model that is based on experimental variables. We have extended the underlying KEfED representation of tract-tracing experiments by incorporating the definition of a neuronanatomical data map as a measurement variable in the study design. This paper describes the software design of a web-application that allows anatomical data sets to be described within a standard experimental context and thus indexed by non-spatial experimental design features.

Sonic hedgehog is required for survival of both myogenic and chondrogenic somitic lineages.

PubMed

Teillet, M; Watanabe, Y; Jeffs, P; Duprez, D; Lapointe, F; Le Douarin, N M

1998-06-01

In vertebrates, the medial moieties of the somites give rise to the vertebrae and epaxial muscles, which develop in close relationship with the axial organs, neural tube and notochord. The lateral moieties contribute to the ribs and to limb and body wall muscles (hypaxial muscles) after a phase of lateral and ventral migration. Surgical ablation of the neural tube and notochord in the chick embryo during segmentation and early differentiation of the somites (day 2 of incubation) does not affect primary development of the hypaxial muscles, but leads to a complete absence of epaxial muscles, vertebrae and ribs, due to cell death in the somites. Here we demonstrate that cell death, which occurs within 24 hours of excision of the axial organs, affects both myogenic and chondrogenic cell lineages defined, respectively, by the expression of MyoD and Pax-1 genes. In contrast, Pax-3 transcripts, normally present in cells giving rise to hypaxial muscles, are preserved in the excised embryos. Backgrafting either the ventral neural tube or the notochord allows survival of MyoD- and Pax-1-expressing cells. Similarly, Sonic hedgehog-producing cells grafted in place of axial organs also rescue MyoD- and Pax-1-expressing cells from death and allow epaxial muscles, ribs and vertebrae to undergo organogenesis. These results demonstrate that the ventral neural tube and the notochord promote the survival of both myogenic and chondrogenic cell lineages in the somites and that this action is mediated by Sonic hedgehog.

The lasting effects of process-specific versus stimulus-specific learning during infancy.

PubMed

Hadley, Hillary; Pickron, Charisse B; Scott, Lisa S

2015-09-01

The capacity to tell the difference between two faces within an infrequently experienced face group (e.g. other species, other race) declines from 6 to 9 months of age unless infants learn to match these faces with individual-level names. Similarly, the use of individual-level labels can also facilitate differentiation of a group of non-face objects (strollers). This early learning leads to increased neural specialization for previously unfamiliar face or object groups. The current investigation aimed to determine whether early conceptual learning between 6 and 9 months leads to sustained behavioral advantages and neural changes in these same children at 4-6 years of age. Results suggest that relative to a control group of children with no previous training and to children with infant category-level naming experience, children with early individual-level training exhibited faster response times to human faces. Further, individual-level training with a face group - but not an object group - led to more adult-like neural responses for human faces. These results suggest that early individual-level learning results in long-lasting process-specific effects, which benefit categories that continue to be perceived and recognized at the individual level (e.g. human faces). © 2014 John Wiley & Sons Ltd.

Neurovascular coupling and energy metabolism in the developing brain

PubMed Central

Kozberg, M.; Hillman, E.

2016-01-01

In the adult brain, increases in local neural activity are almost always accompanied by increases in local blood flow. However, many functional imaging studies of the newborn and developing human brain have observed patterns of hemodynamic responses that differ from adult responses. Among the proposed mechanisms for the observed variations is that neurovascular coupling itself is still developing in the perinatal brain. Many of the components thought to be involved in actuating and propagating this hemodynamic response are known to still be developing postnatally, including perivascular cells such as astrocytes and pericytes. Both neural and vascular networks expand and are then selectively pruned over the first year of human life. Additionally, the metabolic demands of the newborn brain are still evolving. These changes are highly likely to affect early postnatal neurovascular coupling, and thus may affect functional imaging signals in this age group. This chapter will discuss the literature relating to neurovascular development. Potential effects of normal and aberrant development of neurovascular coupling on the newborn brain will also be explored, as well as ways to effectively utilize imaging techniques that rely on hemodynamic modulation such as fMRI and NIRS in younger populations. PMID:27130418

Prenatal arsenic exposure alters REST/NRSF and microRNA regulators of embryonic neural stem cell fate in a sex-dependent manner

PubMed Central

Tyler, Christina R.; Labrecque, Matthew T.; Solomon, Elizabeth R.; Guo, Xun; Allan, Andrea M.

2016-01-01

Exposure to arsenic, a common environmental toxin found in drinking water, leads to a host of neurological pathologies. We have previously demonstrated that developmental exposure to a low level of arsenic (50 ppb) alters epigenetic processes that underlie deficits in adult hippocampal neurogenesis leading to aberrant behavior. It is unclear if arsenic impacts the programming and regulation of embryonic neurogenesis during development when exposure occurs. The master negative regulator of neural-lineage, REST/NRSF, controls the precise timing of fate specification and differentiation of neural stem cells (NSCs). Early in development (embryonic day 14), we observed increased expression of Rest, its co-repressor, CoREST, and the inhibitory RNA binding/splicing protein, Ptbp1, and altered expression of mRNA spliced isoforms of Pbx1 that are directly regulated by these factors in the male brain in response to prenatal 50 ppb arsenic exposure. These increases were concurrent with decreased expression of microRNA-9 (miR-9), miR-9*, and miR-124, all of which are REST/NRSF targets and inversely regulate Rest expression to allow for maturation of NSCs. Exposure to arsenic decreased the formation of neuroblasts in vitro from NSCs derived from male pup brains. The female response to arsenic was limited to increased expression of CoREST and Ptbp2, an RNA binding protein that allows for appropriate splicing of genes involved in the progression of neurogenesis. These changes were accompanied by increased neuroblast formation in vitro from NSCs derived from female pups. Unexposed male mice express transcriptomic factors to induce differentiation earlier in development compared to unexposed females. Thus, arsenic exposure likely delays differentiation of NSCs in males while potentially inducing precocious differentiation in females early in development. These effects are mitigated by embryonic day 18 of development. Arsenic-induced dysregulation of the regulatory loop formed by REST/NRSF, its target microRNAs, miR-9 and miR-124, and RNA splicing proteins, PTBP1 and 2, leads to aberrant programming of NSC function that is perhaps perpetuated into adulthood inducing deficits in differentiation we have previously observed. PMID:27751817

Metacognition in Early Phase Psychosis: Toward Understanding Neural Substrates

PubMed Central

Vohs, Jenifer L.; Hummer, Tom A.; Yung, Matthew G.; Francis, Michael M.; Lysaker, Paul H.; Breier, Alan

2015-01-01

Individuals in the early phases of psychotic illness have disturbed metacognitive capacity, which has been linked to a number of poor outcomes. Little is known, however, about the neural systems associated with metacognition in this population. The purpose of this study was to elucidate the neuroanatomical correlates of metacognition. We anticipated that higher levels of metacognition may be dependent upon gray matter density (GMD) of regions within the prefrontal cortex. Examining whole-brain structure in 25 individuals with early phase psychosis, we found positive correlations between increased medial prefrontal cortex and ventral striatum GMD and higher metacognition. These findings represent an important step in understanding the path through which the biological correlates of psychotic illness may culminate into poor metacognition and, ultimately, disrupted functioning. Such a path will serve to validate and promote metacognition as a viable treatment target in early phase psychosis. PMID:26132568

Play It Again: Neural Responses to Reunion with Excluders Predicted by Attachment Patterns

ERIC Educational Resources Information Center

White, Lars O.; Wu, Jia; Borelli, Jessica L.; Mayes, Linda C.; Crowley, Michael J.

2013-01-01

Reunion behavior following stressful separations from caregivers is often considered the single most sensitive clue to infant attachment patterns. Extending these ideas to middle childhood/early adolescence, we examined participants' neural responses to reunion with peers who had previously excluded them. We recorded event-related potentials…

Neural Indices of Semantic Processing in Early Childhood Distinguish Eventual Stuttering Persistence and Recovery

ERIC Educational Resources Information Center

Kreidler, Kathryn; Wray, Amanda Hampton; Usler, Evan; Weber, Christine

2017-01-01

Purpose: Maturation of neural processes for language may lag in some children who stutter (CWS), and event-related potentials (ERPs) distinguish CWS who have recovered from those who have persisted. The current study explores whether ERPs indexing semantic processing may distinguish children who will eventually persist in stuttering…

On the balance of envelope and temporal fine structure in the encoding of speech in the early auditory system.

PubMed

Shamma, Shihab; Lorenzi, Christian

2013-05-01

There is much debate on how the spectrotemporal modulations of speech (or its spectrogram) are encoded in the responses of the auditory nerve, and whether speech intelligibility is best conveyed via the "envelope" (E) or "temporal fine-structure" (TFS) of the neural responses. Wide use of vocoders to resolve this question has commonly assumed that manipulating the amplitude-modulation and frequency-modulation components of the vocoded signal alters the relative importance of E or TFS encoding on the nerve, thus facilitating assessment of their relative importance to intelligibility. Here we argue that this assumption is incorrect, and that the vocoder approach is ineffective in differentially altering the neural E and TFS. In fact, we demonstrate using a simplified model of early auditory processing that both neural E and TFS encode the speech spectrogram with constant and comparable relative effectiveness regardless of the vocoder manipulations. However, we also show that neural TFS cues are less vulnerable than their E counterparts under severe noisy conditions, and hence should play a more prominent role in cochlear stimulation strategies.

Understanding behavioral effects of early life stress using the reactive scope and allostatic load models

PubMed Central

HOWELL, BRITTANY R.; SANCHEZ, MAR M.

2015-01-01

The mechanisms through which early life stress leads to psychopathology are thought to involve allostatic load, the “wear and tear” an organism is subjected to as a consequence of sustained elevated levels of glucocorticoids caused by repeated/prolonged stress activations. The allostatic load model described this phenomenon, but has been criticized as inadequate to explain alterations associated with early adverse experience in some systems, including behavior, which cannot be entirely explained from an energy balance perspective. The reactive scope model has been more recently proposed and focuses less on energy balance and more on dynamic ranges of physiological and behavioral mediators. In this review we examine the mechanisms underlying the behavioral consequences of early life stress in the context of both these models. We focus on adverse experiences that involve mother–infant relationship disruption, and dissect those mechanisms involving maternal care as a regulator of development of neural circuits that control emotional and social behaviors in the offspring. We also discuss the evolutionary purpose of the plasticity in behavioral development, which has a clear adaptive value in a changing environment. PMID:22018078

Music and speech listening enhance the recovery of early sensory processing after stroke.

PubMed

Särkämö, Teppo; Pihko, Elina; Laitinen, Sari; Forsblom, Anita; Soinila, Seppo; Mikkonen, Mikko; Autti, Taina; Silvennoinen, Heli M; Erkkilä, Jaakko; Laine, Matti; Peretz, Isabelle; Hietanen, Marja; Tervaniemi, Mari

2010-12-01

Our surrounding auditory environment has a dramatic influence on the development of basic auditory and cognitive skills, but little is known about how it influences the recovery of these skills after neural damage. Here, we studied the long-term effects of daily music and speech listening on auditory sensory memory after middle cerebral artery (MCA) stroke. In the acute recovery phase, 60 patients who had middle cerebral artery stroke were randomly assigned to a music listening group, an audio book listening group, or a control group. Auditory sensory memory, as indexed by the magnetic MMN (MMNm) response to changes in sound frequency and duration, was measured 1 week (baseline), 3 months, and 6 months after the stroke with whole-head magnetoencephalography recordings. Fifty-four patients completed the study. Results showed that the amplitude of the frequency MMNm increased significantly more in both music and audio book groups than in the control group during the 6-month poststroke period. In contrast, the duration MMNm amplitude increased more in the audio book group than in the other groups. Moreover, changes in the frequency MMNm amplitude correlated significantly with the behavioral improvement of verbal memory and focused attention induced by music listening. These findings demonstrate that merely listening to music and speech after neural damage can induce long-term plastic changes in early sensory processing, which, in turn, may facilitate the recovery of higher cognitive functions. The neural mechanisms potentially underlying this effect are discussed.

Harmonics added to a flickering light can upset the balance between ON and OFF pathways to produce illusory colors.

PubMed

Rider, Andrew T; Henning, G Bruce; Eskew, Rhea T; Stockman, Andrew

2018-04-24

The neural signals generated by the light-sensitive photoreceptors in the human eye are substantially processed and recoded in the retina before being transmitted to the brain via the optic nerve. A key aspect of this recoding is the splitting of the signals within the two major cone-driven visual pathways into distinct ON and OFF branches that transmit information about increases and decreases in the neural signal around its mean level. While this separation is clearly important physiologically, its effect on perception is unclear. We have developed a model of the ON and OFF pathways in early color processing. Using this model as a guide, we can produce imbalances in the ON and OFF pathways by changing the shapes of time-varying stimulus waveforms and thus make reliable and predictable alterations to the perceived average color of the stimulus-although the physical mean of the waveforms does not change. The key components in the model are the early half-wave rectifying synapses that split retinal photoreceptor outputs into the ON and OFF pathways and later sigmoidal nonlinearities in each pathway. The ability to systematically vary the waveforms to change a perceptual quality by changing the balance of signals between the ON and OFF visual pathways provides a powerful psychophysical tool for disentangling and investigating the neural workings of human vision. Copyright © 2018 the Author(s). Published by PNAS.

Digestive tract neural control and gastrointestinal disorders in cerebral palsy.

PubMed

Araújo, Liubiana A; Silva, Luciana R; Mendes, Fabiana A A

2012-01-01

To examine the neural control of digestive tract and describe the main gastrointestinal disorders in cerebral palsy (CP), with attention to the importance of early diagnosis to an efficient interdisciplinary treatment. Systematic review of literature from 1997 to 2012 from Medline, Lilacs, Scielo, and Cochrane Library databases. The study included 70 papers, such as relevant reviews, observational studies, controlled trials, and prevalence studies. Qualitative studies were excluded. The keywords used were: cerebral palsy, dysphagia, gastroesophageal reflux disease, constipation, recurrent respiratory infections, and gastrostomy. The appropriate control of the digestive system depends on the healthy functioning and integrity of the neural system. Since CP patients have structural abnormalities of the central and peripheral nervous system, they are more likely to develop eating disorders. These range from neurological immaturity to interference in the mood and capacity of caregivers. The disease has, therefore, a multifactorial etiology. The most prevalent digestive tract disorders are dysphagia, gastroesophageal reflux disease, and constipation, with consequent recurrent respiratory infections and deleterious impact on nutritional status. Patients with CP can have neurological abnormalities of digestive system control; therefore, digestive problems are common. The issues raised in the present study are essential for professionals within the interdisciplinary teams that treat patients with CP, concerning the importance of comprehensive anamnesis and clinical examination, such as detailed investigation of gastrointestinal disorders. Early detection of these digestive problems may lead to more efficient rehabilitation measures in order to improve patients' quality of life.

The role of early life nutrition in the establishment of gastrointestinal microbial composition and function

PubMed Central

Davis, Erin C.; Wang, Mei; Donovan, Sharon M.

2017-01-01

ABSTRACT The development of the human infant intestinal microbiota is a sequential process that begins in utero and continues during the first 2 to 3 years of life. Microbial composition and diversity are shaped by host genetics and multiple environmental factors, of which diet is a principal contributor. An understanding of this process is of clinical importance as the microbiota acquired in early life influence gastrointestinal, immune and neural development, and reduced microbial diversity or dysbiosis during infancy is associated with disorders in infancy and later childhood. The goal of this article was to review the published literature that used culture-independent methods to describe the development of the gastrointestinal microbiota in breast- and formula-fed human infants as well as the impact of prebiotic and probiotic addition to infant formula, and the addition of solid foods. PMID:28068209

Oxytocin mediates early experience-dependent cross-modal plasticity in the sensory cortices.

PubMed

Zheng, Jing-Jing; Li, Shu-Jing; Zhang, Xiao-Di; Miao, Wan-Ying; Zhang, Dinghong; Yao, Haishan; Yu, Xiang

2014-03-01

Sensory experience is critical to development and plasticity of neural circuits. Here we report a new form of plasticity in neonatal mice, where early sensory experience cross-modally regulates development of all sensory cortices via oxytocin signaling. Unimodal sensory deprivation from birth through whisker deprivation or dark rearing reduced excitatory synaptic transmission in the correspondent sensory cortex and cross-modally in other sensory cortices. Sensory experience regulated synthesis and secretion of the neuropeptide oxytocin as well as its level in the cortex. Both in vivo oxytocin injection and increased sensory experience elevated excitatory synaptic transmission in multiple sensory cortices and significantly rescued the effects of sensory deprivation. Together, these results identify a new function for oxytocin in promoting cross-modal, experience-dependent cortical development. This link between sensory experience and oxytocin is particularly relevant to autism, where hypersensitivity or hyposensitivity to sensory inputs is prevalent and oxytocin is a hotly debated potential therapy.

Neural attention and evaluative responses to gay and lesbian couples.

PubMed

Dickter, Cheryl L; Forestell, Catherine A; Mulder, Blakely E

2015-01-01

The goal of the current study was to examine whether differential neural attentional capture and evaluative responses for out-group homosexual relative to in-group heterosexual targets occur during social categorization. To this end, 36 heterosexual participants were presented with pictures of heterosexual and homosexual couples in a picture-viewing task that was designed to assess implicit levels of discomfort toward homosexuality and explicit evaluations of pleasantness toward the images. Neural activity in the form of electroencephalogram was recorded during the presentation of the pictures, and event-related potentials resulting from these stimuli were examined. Participants also completed questionnaires that assessed the degree to which they socialized with gays and lesbians. Results demonstrated that relative to straight couples, larger P2 amplitude was observed in response to gay but not to lesbian couples. However, both gay and lesbian couples yielded a larger late positive potential than straight couples. Moreover, the degree to which participants differentially directed early neural attention to out-group lesbian versus in-group straight couples was related to their familiarity with homosexual individuals. This work, which provides an initial understanding of the neural underpinnings of attention toward homosexual couples, suggests that differences in the processing of sexual orientation can occur as early as 200 ms and may be moderated by familiarity.